research article single nucleotide polymorphisms in ...research article single nucleotide...

Research ArticleSingle Nucleotide Polymorphisms in Pediatric IdiopathicNephrotic Syndrome

Maija Suvanto1 Timo Jahnukainen1 Marjo Kestilauml2 and Hannu Jalanko1

1Childrenrsquos Hospital University of Helsinki and Helsinki University Hospital 00290 Helsinki Finland2Department of Chronic Disease Prevention National Institute for Health and Welfare 00271 Helsinki Finland

Correspondence should be addressed to Maija Suvanto maijasuvantohelsinkifi

Received 11 January 2016 Accepted 5 April 2016

Academic Editor Kazunari Kaneko

Copyright copy 2016 Maija Suvanto et al This is an open access article distributed under the Creative Commons Attribution Licensewhich permits unrestricted use distribution and reproduction in any medium provided the original work is properly cited

Polymorphic variants in several molecules involved in the glomerular function and drug metabolism have been implicated in thepathophysiology of pediatric idiopathic nephrotic syndrome (INS) but the results remain inconsistentWe analyzed the associationof eleven allelic variants in eight genes (angiopoietin-like 4 (ANGPTL4) glypican 5 (GPC5) interleukin-13 (IL-13) macrophagemigration inhibitory factor (MIF) neural nitric oxide synthetase (nNOS) multidrug resistance-1 (MDR1) glucocorticoid-inducedtranscript-1 (GLCCI1) and nuclear receptor subfamily-3 (NR3C1)) in 100 INS patients followed up till adulthood We genotypedvariants using PCR and direct sequencing and evaluated estimated haplotypes of MDR1 variants The analysis revealed fewdifferences in SNP genotype frequencies between patients and controls or in clinical parameters among the patients Genotypedistribution of MDR1 SNPs rs1236 rs2677 and rs3435 showed significant (119901 lt 005) association with different medication regimes(glucocorticoids only versus glucocorticoids plus additional immunosuppressives) Some marginal association was detectedbetween ANGPTL4 GPC5 GLCCI1 and NR3C1 variants and different medication regimes number of relapses and age of onsetConclusion While MDR1 variant genotype distribution associated with different medication regimes the other analyzed genevariants showed only little or marginal clinical relevance in INS

1 Introduction

Childhood-onset idiopathic nephrotic syndrome (INS) isa common kidney disease in children It is characterizedby minimal glomerular changes in light microscopy andpodocyte foot process effacement in electronmicroscopyThegreat majority (80ndash90) of INS patients show good respon-siveness to steroid treatment but recurrent episodes occurin at least 70 of the patients Development of renal failureoccurs rarely

The pathophysiology of INS is still unknown During thepast few years polymorphic variants of several moleculesinvolved in the glomerular function have been analyzed inINS patients and animal models of proteinuria to discovergenetic components that would participate in the devel-opment of disease or modify its phenotype These includeangiopoietin-like 4 (Angptl4) glycoprotein which is upreg-ulated in rats with steroid sensitive proteinuria [1 2]

interleukin-13 (IL-13) a cytokine that alters podocyte func-tion and is reported to be upregulated in patients withactive INS [3 4] macrophage migration inhibitory factor(MIF) a proinflammatory cytokine and counter regulatorof the immunosuppressive effects of glucocorticoids [5 6]glypican-5 gene (GPC5) which encodes a podocyte cellsurface proteoglycan whose variants are associated with apodocyte injury and proteinuria [7] and neural nitric oxidesynthetase (nNOS) that plays a role in glomerular hyperper-meability [8]

In addition to the five functional molecules there arereports on the association of INS with polymorphic variantsof molecules involved in the glucocorticoid metabolismThese include multidrug resistance-1 gene (MDR1) encodingP-glycoprotein-170 (P-gp) which transports steroids acrossthe cell membranes [9ndash12] nuclear receptor subfamily-3gene (NR3C1) that encodes cytosolic glucocorticoid receptor(GR) [13 14] and glucocorticoid-induced transcript 1 gene

Hindawi Publishing CorporationInternational Journal of NephrologyVolume 2016 Article ID 1417456 12 pageshttpdxdoiorg10115520161417456

2 International Journal of Nephrology

Table 1 Primer sequences 119879119898 annealing temperature

Gene SNP Forward 51015840-31015840 Reverse 51015840-31015840 119879119898(∘C)

Angptl4 rs1044250 (c797CgtT) CTACAAGGCGGGGTTTGGGGAT AAGTGGAGAAGGGTACGGAGAGGCC 62

GPC5 rs16946160(c325+1026376GgtA) AGAGTTGACAAGAGTTAAACAGCA GTCATCTCTGACTCCGCAGTAT 58

IL-13 rs848 (clowast526CgtA) GTTTGTCACCGTTGGGGATTGG CAATGTCCCCTCCCCCAGTGTT 62MIF rs755622 (c-270GgtC) CTAAGAAAGACCCGAGGCGA GGCACGTTGGTGTTTACGAT 58nNOS rs2662826 (clowast276CgtT) ACTCCTTGAGTTTTCCTGCTGCGA CCATGTTCCAGTGGTTTCATGCACCC 62

MDR1

rs1128503 (c1236CgtT) TATCCTGTGTCTGTGAATTGCC CTGACTCACCACACCAATG 62rs2032582

(c2677GgtTA) TGCAGGCTATAGGTTCCAGG TTTAGTTTGACTCACCTTCCCG 60

rs1045642 (c3435CgtT) TGTTTTCAGCTGCTTGATGG AAGGCATGTATGTTGGCCTC 58

GLCCI1rs37972 (c-1473TgtC) GACCCCTGCATATAGTGCCT AATGAAACTGAAAGCGTACAAAGA 58rs37973 (c-1106GgtA) AATTCCTTGTTGACCCCTGC AGCTGAGTTTTCGTGACCAG 62

NR3C1 rs41423247(c1184+646CgtG) AAATTGAAGCTTAACAATTTTGGC GCAGTGAACAGTGTACCAGACC 58

(GLCCI1) that encodes Glcci1 protein that associated withglucocorticoid (GC) responsiveness and development ofproteinuria in animal models [15 16]

In this study we genotyped eleven single nucleotide poly-morphisms (SNPs) from the above mentioned eight genesfrom DNA samples obtained from a unique cohort of INSpatients followed up over 30 years The results show that thevariants in the genes coding for functional kidney proteinshave little clinical relevance in INS while variants in genesinvolved in glucocorticoid metabolism show marginal asso-ciation with INS The genotype distribution of MDR1 SNPsshows significant association with medication regime as theminor alleles of the SNPs are more frequent in patients whoreceive immunosuppressive medication in addition to gluco-corticoids

2 Materials and Methods

21 Patients The study cohort included 100 INS patients ofwhom 83were diagnosed within 1965ndash1981 at theHospital forChildren and Adolescents University of Helsinki These 83patients were enrolled in the International Study of KidneyDisease in Children (ISKDC) and were treated by protocolsstill used in pediatric nephrology The mean age at the lastfollow-up was 350 years (range 251ndash441 years) Clinical datawere carefully recorded from the patient records as was pre-viously reported in detail [17]The remaining 17 patients werediagnosed more recently at the Hospital for Children andAdolescents University of Helsinki and were still children oradolescents of them SNP genotypes were used in statisticalcomparison between INS patients and controls A bloodsample for DNA extraction was gathered from all

The controls included a cohort of 101 subjects who wereeither healthy adults or suffered from nonkidney relatedcondition

22 SNPs and PCR Analysis We selected eleven SNPsfrom eight genes to this study based on previous reportsin literature on their association with INS The genes and

SNPs were Angptl4 SNP rs1044250 (c797CgtT) GPC5SNP rs16946160 (c325+102637GgtA) IL-13 SNP rs848(clowast526CgtA) MIF rs755622 (c-270GgtC) nNOS rs2682826(clowast276CgtT)MDR1 SNPs rs1128503 (c1236CgtT) rs2032582(c2677GgtTA) rs1045642 (c3435CgtT) GLCC11 SNPsrs37972 (c-1473CgtT) and rs37973 (c-1106AgtG) and NR3C1rs41423247 (c1184+646GgtC) Analysis was carried out usingdirect sequencing Exons were amplified by PCR withflanking intronic primers and the reactions were performedin total volumes of 25120583L as previously described [18]Occasionally the denaturation temperature was raised upto 98∘C or betaine was added to the reaction mixturePCR products were genotyped using automated sequenceanalysis by BigDye-terminator chemistry (v31) on GeneticAnalyzer 3730 (Applied Biosystems) The sequences wereanalyzed with GeneComposer version 1101051 (httpwwwGeneComposercom) The genotypes were comparedbetween patients and controls and among various clinicalvariables that include age of onset (lt3 yr versus gt3 yr)number of relapses (lt5 versus gt5) frequent relapses(no versus yes) response to GC (normal versus slownoresponse) treatment (only GC versus GC together withimmunosuppressive (IS) drugs) and GC dependence (noversus yes)

The genotypes of the threeMDR1 variants (rs1236 rs2677and rs3435) were used to carry out a haplotype analysisTwelve haplotypes were derived from the genotype data usingthe program PHASE (v21) [19 20] The estimated MDR1haplotype frequencies were compared between patients andcontrols and among various clinical variables

All primers are presented in Table 1 Most of the primersequences are gathered from literature Angptl4 rs1044250[21] IL-13 rs848 [4] MIF rs755622 [22] nNOS rs2682826[8] MDR1 rs1128503 rs2032582 rs1045642 [9] and NR3C1rs41423247 [23] Primers for GLCC11 (NM 138426) rs37972and rs37973 and GPC5 (NM 004466) rs16946160 weredesigned using primer3 program (httpwwwncbinlmnihgovtoolsprimer-blast)

International Journal of Nephrology 3

23 Statistics The statistical analysis was carried out usingstatistical software JMP 10 (httpwwwjmpcom SAS insti-tute Inc Cary NC USA) Logistic regression analysis wasused to calculate odds ratios (OD) and 95 confidenceintervals (CI) for the association between genotypes andthe risk of INS The difference between selected clinicalvariables and genotypes was determined by Fisherrsquos exact testStatistical significance was defined as 119901 lt 005

24 Ethics All patients or their parents were informed of thecontent of the study and they signed a form of consent TheEthics Committee of the Childrenrsquos Hospital University ofHelsinki approved the study (IRB HUS509E705)

3 Results

Eleven SNPs from eight genes encoding proteins related tokidney function and steroid metabolism (Angptl4 GPC5MIF nNOS IL-13 MDR1 and NR3C1 GLCCl1) were ana-lyzed from 100 INS patients The distribution of observedgenotypes was consistent with those expected under theassumptions of the Hardy-Weinberg Equilibrium (119901 ge 005)(Table 2)

Comparison of the frequencies of the 11 SNPs betweenINS patients and controls was made and is presented inTable 3 No association between variants and disease statuswas observed except in rs848 variant in IL-13 gene where het-erozygotic genotype showed difference in frequency betweenpatients and controls (53 versus 38 OR 2025 CI 1095ndash3785 and 119901 = 00243)

Comparison of the SNP genotype frequencies amongINS patients with various clinical parameters is presented inTables 4 and 5 These variables included age of onset (lt3 yrversus gt3 yr) number of relapses (lt5 versus gt5) frequentrelapses (no versus yes) response to GC (normal versusslowno response) treatment (only GC versus GC togetherwith immunosuppressive (IS) drugs) and GC dependence(no versus yes)

Few clinically relevant correlations were found in relationto the SNPs in genes IL13 MIF and nNOS Angptl4 SNPrs1044250 alleleCwasmore frequent in patientswho receivedISmedication in addition toGCs compared to thosewho onlyreceived GCs (72 versus 56 119901 = 00228) In GPC5 SNPrs16946160A allele wasmore frequent in patientswith diseaseonset less than three years of age than in those with diseaseonsetmore than three years of age (16 versus 5119901 = 00421)

The genotype distribution in MDR1 SNPs showed differ-ence in patients who received only GCs compared to thosewho also received IS medication as allele T frequency washigher in the latter group in rs1128503 (706 versus 286119901 = 00012) in rs2032582 (679 versus 429 119901 = 00028)and in rs1045642 (731 versus 524 119901 = 00092) SimilarlyinGLCCI1 SNP rs37973A allele wasmore frequent in patientswho received IS medication (67 versus 50 119901 = 00387)Patients with more than five relapses also had GLCCI1 SNPrs37973 A allele more frequently than those with fewerrelapses (70 versus 52 119901 = 00377) A curious findingwas that NR3C1 SNP rs41423247 heterozygous GC genotypewas more frequent in patients with more than five relapses

(68 versus 327) and in patients with frequent relapses (60versus 34)

Haplotype analysis of the three MDR1 variants (rs1236rs2677 and rs3435) revealed twelve estimated haplotypesamong cases and controlsThese data are presented inTable 6Curiously the patient samples were less varied as the allelefrequency of the two most common haplotypes TTT andCGC was 70 (422 and 275 resp) while in the controlsamples it took the four most common haplotypes TTTCGC CTT and TGT to achieve the same (234 186 156and 126 resp) Most of the haplotypes had 119901 lt 005Thedistribution of the allele frequencies of the haplotypes amongclinical variables showed no significant difference betweengroups with the exception of the comparison betweenpatients with less than five relapses and patients with morethan five relapses as is seen in Table 6 In other variants onlyTTT and CGC haplotypes had allele frequency higher than10 in any of the variables and the combined allele frequencyof these two varied between 71 and 867

4 Discussion

The discovery of causative or disease modifying geneticfactors underlying INS is of great interest and could have aprofound clinical impact In this study we genotyped elevenSNPs from eight genes that had previously been studied inrelation to INS and proteinuric animal modelsWe comparedthe SNP frequencies in INS patients and controls as wellas in the subgroups of INS patients Very little alterationwas detected in the distribution of SNPs between patientsand controls and only marginal differences were observedamong the INS subgroups in the Angptl4 GPC5MDR1 andNR3C1 genes An exception is the genotype distribution ofMDR1 SNPs in patients who receiveGCmedication and thosewho also receive IS as the T alleles are more frequent in thelatter group Summation of the findings of this study and acomparison to other recent studies can be found in Table 7

Angptl4 is a secretory protein involved in lipidmetabolism and its increased expression has been observedin podocytes and circulation in human and experimentalINS [24 25] The genetic variant SNP rs1044250 in exon 6leads to amino acid change pT266M and the homozygousC genotype of this variant has been associated with lowerplasma Angptl4 levels [26] Recently Clement et al [2]discovered that increases in circulating Angptl4 reducedproteinuria but at the cost of inducing hypertriglyceridemiaIn our analysis pT266M genotype was not associated withthe occurrence of INS disease or clinical severity of thedisorder However the C allele was more frequent [72 versus54] in patients who received IS drug medication instead ofGCs only

Recently Okamoto et al [7] identified an associationbetween variants of glypican-5 (GPC5) gene and acquiredNS (focal segmental glomerulosclerosis proteinuric IgA-nephropathy) through a genome wide association study andreplication analysis They showed that glypican-5 is localizedon podocyte cell surface membranes and that the risk geno-type (AA) of the GPC5 SNP rs16946160 was associated withhigher expression In our study we observed an association


Table 2 The distribution of observed and expected genotypes 119901 values of 005 or above signal consistency with the assumptions of theHardy-Weinberg Equilibrium

Gene SNP Genotype Patients ControlsObserved Expected 120594

2

119901 Observed Expected 1205942

119901

Angptl4 rs1044250 (c797CgtT)CC 35 336 031 gt005 30 223 014 gt005CT 46 487 39 420TT 19 176 15 197

GPC5 rs16946160(c325+1026376GgtA)

GG 88 884 041 gt005 86 856 025 gt005GA 12 113 14 147AA 0 04 1 06

IL13 rs848 (clowast526CgtA)CC 31 331 071 gt005 45 406 363 gt005CA 53 489 38 469AA 16 181 18 136

MIF rs755622 (c-270GgtC)GG 61 608 001 gt005 63 595 388 119901 = 005GC 34 343 29 361CC 5 48 9 55

nNOS rs2662826 (clowast276CgtT)CC 49 490 00 gt005 52 488 238 gt005CT 42 420 35 414TT 9 90 12 88

MDR1

rs1128503 (c1236CgtT)CC 22 235 037 gt005 23 211 058 gt005CT 53 500 45 488TT 25 265 30 281

rs2032582(c2677GgtTA)

GG 17 194 166 gt005 24 235 036 gt005GT 49 458 45 465TT 26 270 24 230TA 3 42 2 24GA 5 35 3 24AA 0 02 0 01


GLCCI1

rs37972 (c-1473TgtC)CC 35 354 003 gt005 25 290 263 gt005CT 49 482 56 481TT 16 164 16 200

rs37973 (c-1106GgtA)AA 33 336 007 gt005 24 278 260 gt005GA 50 487 52 444GG 17 176 14 178

NR3C1 rs41423247(c1184+646CgtG)

GG 32 308 024 gt005 37 342 153 gt005GC 47 494 37 426CC 21 198 16 132

between rs16946160 A allele and early disease onset (16 versus5) but we did not find an association between this SNPand INS in general It is however notable that none of ourpatients and only one of the controls carried theAAgenotypeOkamoto et al found the A allele frequency of controls to be0168 and dbSNP (httpwwwncbinlmnihgovsnp) puts itat 0161 In our study it was only 008 Thus it is possiblethat due to the frequency differences between populations theassociation between the risk genotype and INS is not visiblein our patients

Alasehirli et al [8] found that in nNOS gene poly-morphism rs2682826 the TT genotype was associated withINS but not with GC responsiveness NO attenuates manyfunctions in the kidney and all forms ofNOS are expressed inthe kidney but the role ofNO in renal disease is unclear In ourstudy we did not find an association of rs2682826 genotypeswith INS or with any clinical features of the disease

Our results of the two cytokines IL-13 and MIF whosegenetic variants have been associated with NS were alsonegative While Wei et al [4] reported that 31015840UTR SNPs


Table 3 Comparison of patient and control genotype distribution OR odds ratio CI confidence interval 119901 values lower than 005 aremarked with lowast

Gene SNP Genotype Patients () Controls () OR (95 CI) 119901

119899 = 100 119899 = 84

Angptl4 rs1044250 (c797CgtT)

CC 35 (35) 30 (36) ReferenceCT 46 (46) 39 (46) 101 (053minus193) 0974TT 19 (19) 15 (18) 109 (047minus253) 0847C 116 (58) 99 (589) ReferenceT 84 (42) 69 (411) 104 (069minus158) 0857

119899 = 100 119899 = 101

GPC5 rs16946160(c325+1026376GgtA)

GG 88 (88) 86 (85) ReferenceGA 12 (12) 14 (14) 084 (036minus192) 0674AA 0 (0) 1 (1) 6 times 10

minus7 (0minus575) 0236G 188 (94) 186 (921) ReferenceA 12 (6) 16 (79) 074 (034minus160) 0449

119899 = 100 119899 = 101

IL13 rs848 (clowast526CgtA)

CC 31 (31) 45 (45) ReferenceCA 53 (53) 38 (38) 203 (110minus379) 0024lowast

AA 16 (16) 18 (18) 129 (057minus292) 0540C 115 (575) 126 (63) ReferenceA 85 (425) 74 (37) 126 (084minus189) 0261

119899 = 100 119899 = 101

MIF rs755622 (c-270GgtC)

GG 61 (61) 63 (62) ReferenceGC 34 (34) 29 (29) 121 (066minus223) 0537CC 5 (5) 9 (9) 057 (017minus176) 0335G 156 (78) 155 (767) ReferenceC 44 (22) 47 (233) 093 (058minus149) 0761

119899 = 100 119899 = 99

nNOS rs2662826(clowast276CgtT)


119899 = 100 119899 = 98

MDR1

rs1128503(c1236CgtT)


119899 = 100 119899 = 98

rs2032582(c2677GgtTA)

GG 17 (17) 24 (24) ReferenceGT 49 (49) 45 (45) 154 (074minus326) 0253TT 26 (26) 24 (24) 153 (067minus355) 0316TA 3 (3) 2 (2) 212 (032minus1742) 0432GA 5 (5) 3 (3) 235 (051minus1275) 0274G 88 (44) 96 (49) ReferenceT 104 (52) 95 (485) 119 (080minus179) 0386A 8 (4) 5 (26) 175 (056minus596) 0338

119899 = 100 119899 = 98

rs1045642(c3435CgtT)

CC 13 (13) 10 (10) ReferenceCT 49 (49) 53(54) 0711 (028minus176) 0462TT 38 (38) 35 (36) 084 (032minus214) 0708C 75 (375) 73 (372) ReferenceT 125 (625) 123 (628) 099 (066minus149) 0958


Table 3 Continued


119899 = 100 119899 = 97

GLCCI1

rs37972 (c-1473TgtC)


119899 = 100 119899 = 90

rs37973 (c-1106GgtA)

AA 33 (33) 24 (27) ReferenceGA 50 (50) 52 (58) 070 (036minus134) 0282GG 17 (17) 14 (16) 088 (037minus215) 0782A 116 (58) 100 (556)G 84 (42) 80 (444) 091 (060minus136) 0631

119899 = 100 119899 = 90

NR3C1 rs41423247(c1184+646CgtG)


of the IL-13 gene correlate with long term outcome of INSwe did not see any association between the analyzed SNPand the number of relapses response to medication or anyother featureMIF is counterregulated by glucocorticoids andthe rs755622 SNPs have been studied in association withNS Vivarelli et al [6] found that the frequency of C allelewas higher in Italian patients than in controls and higherin steroid resistant NS (SRNS) than in steroid sensitive NS(SSNS) Similarly Berdeli et al [5] found that GC genotypeand C allele were higher in patients than in controls and CCgenotype was more frequent in patients with SRNS than inthose with SSNS On the other hand Choi et al [22] did notsee this association in Korean patients Similarly our studydid not reveal any association between rs755622 SNP and INSor any of the clinical parameters

MDR-1 gene codes for a membranous P-gp which isa multidrug transporter expressed in the proximal tubulecells Certain SNPs in MDR1 gene are believed to affect theexpression of the gene or activity of the protein it codesThe common SNP rs1045642 in exon 26 has garnered alot of attention It is synonymously variant and it has beensuggested that it is not causal itself but linked with anotherpolymorphism or has an effect on DNA structure or RNAstability [12] Of the other two common SNPs includedin this study rs2032582 does lead to amino acid changeAla899SerThr This change could possibly increase the drugresistance of the cell [27 28] The data on the significance ofthese SNPs from different studies are contradictory The dis-tribution of rs2032582 genotypeswas found to be significantlydifferent in healthy controls compared to patients in Indianand Egyptian populations [11 12] while studies in Polish andKorean subjects did not find the association [9 22]

We did not find any difference in the Finnish patientsand controls in rs2032582 genotypes Wasilewska et al [9]

Jafar et al [11] and Youssef et al [12] found an associationbetween rs1045642 and NS (allele T and genotype TT werehigher in patients) while Choi et al [22] did not All thesubjects in these studies come from different populationsthus it is possible that the difference in results is due togenetic heterogeneity among populations Youssef et al [12]compared rs1045642 allele frequencies in their Egyptiancontrol subjects and found that the frequencies (C 664 T336) were consistent with frequencies previously reportedin African populations but different from frequencies foundin Caucasian Asian and Indian populations [11 29] In ourstudy these frequencies were nearly the opposite (C 372T 628) of those determined by Youssef et al [12] Thismay affect the association between rs1045642 genotypes andNS that was observed in Egyptian population but not inFinnish population Also in our study population MDR1SNP rs1045642 CC genotype showed association with higherage of onset (20 versus 0) Youssef et al reported similarassociation for SNPS rs2032582 as well as rs1045642 Otherstudies did not show this association [9 22]

In our study all three MDR1 SNPs showed associationwith treatment choices T allele and TT genotype being morecommon in patients who needed IS drugs compared to thosewho were only medicated with GCs which indicates thatT and TT are associated with more complicated form ofthe disease Surprisingly only rs1045642 showed significantassociation between genotype distribution and GC respon-siveness (T allele was more frequent in poor responders)although it must be noted that only ten of our patients werenot responsive to GCs this small cohort size may affect theseresults

We carried out haplotype analysis of the three MDR1variants In previous studies Wasilewska et al [9] reportedsignificant association of haplotype frequencies with steroid


Table4Com

paris

onof

geno

type

andallelefre

quencies

offunctio

nalkidneygene

varia

ntsa

ndselected

clinicalfeatures119901values

lower

than

005

arem

arkedwithlowast

Gene

SNP

Genotype

Relap

ses

Frequent

relap

ser()

Age

ofon

set()

Respon

seto

steroids

Treatm

ent

lt5

gt5119901

No

Yes119901

lt3gt3

119901Normal

Slow

NR119901

OnlyGC

IS119901

119899=52119899=25

119899=41119899=40

119899=16119899=65

119899=67119899=13

119899=42119899=39

Angptl4

rs1044

250(c797Cgt

T)

CC20

(38)

11(44)

09426

14(34)

18(44)

04133

8(50)

24(37)

03311

25(37)

6(46)

08494

12(29)

20(51)

00679

CT25

(48)

11(44)

19(46)

18(44)

6(38)

31(48)

32(48)

5(38)

21(50)

16(41)

TT7(13)

3(12)

8(20)

4(10)

2(13)

10(15)

10(15)

2(15)

9(21)

3(8)

C65

(625)

33(66)

07230

47(57)

54(68)

01977

22(69)

79(61)

05416

82(61)

17(65)

08094

45(54)

56(72)

002

28lowast

T39

(375

)17

(34)

35(43)

26(33)

10(31)

51(39)

52(39)

9(35)

39(46)

22(28)

GPC

5rs16946160

(c32

5+1026376GgtA)

GG

47(90)

20(80)

02789

37(90)

33(83)

03493

11(69)

59(91)

00359lowast

58(87)

11(85)

1000

38(90)

32(82)

03389

GA

5(10)

5(20)

4(10)

7(18)

5(31)

6(9)

9(13)

2(15)

4(10)

7(18)

AA

0(0)

0(0)

0(0)

0(0)

0(0)

0(0)

0(0)

0(0)

0(0)

0(0)

G99

(95)

45(90)

02951

78(95)

73(91)

03663

27(84)

124(95)

00421lowast

125(93)

24(92)

06322

80(95)

71(91)

03567

A5(5)

5(10)

4(5)

7(9)

5(16)

6(5)

9(7)

2(8)

4(5)

7(9)

IL13

rs848(clowast526CgtA)

CC18

(35)

8(32)

08456

10(24)

16(40)

03114

7(44)

19(29)

064

2024

(36)

2(15)

03703

15(36)

11(28)

07568

CA25

(48)

14(56)

24(59)

19(48)

7(44)

35(54)

33(49)

9(69)

21(50)

21(54)

AA

9(17)

3(12)

7(17)

5(13)

2(13)

11(17)

10(15)

2(15)

6(14

)7(18)

C61

(59)

30(60)

1000

44(54)

51(64)

02056

21(66)

73(56)

04246

81(60)

13(50)

1000

51(61)

43(55)

05253

A43

(41)

20(40)

38(46)

29(36)

11(34)

57(44)

53(40)

13(50)

33(39)

35(45)

MIF

rs755622

(c-2

70GgtC)

GG

31(60)

16(64)

1000

26(63)

24(60)

09284

9(56)

40(62)

00634

40(60)

8(62)

1000

25(60)

24(62)

07481

GC

18(35)

8(32)

13(32)

14(35)

7(44)

21(32)

23(34)

5(38)

14(33)

14(36)

CC3(6)

1(4)

2(5)

2(5)

0(0)

4(6)

4(6)

0(0)

3(7)

1(3)

G80

(77)

40(80)

08359

65(79)

62(78)

08497

25(78)

101(78)

1000

103(77)

21(81)

1000

64(76)

62(79)

07063

C24

(23)

10(20)

17(21)

18(23)

7(22)

29(22)

31(23)

5(19)

20(24)

16(21)

nNOS

rs2662826

(clowast276CgtT)

CC24

(46)

10(4)

07393

19(46)

17(43)

02027

5(31)

31(48)

040

8029

(43)

7(54)

06178

19(45)

17(44)

05406

CT23

(44)

11(44)

20(49)

16(40

8(50)

28(43)

31(46)

4(31)

20(48)

16(41)

TT5(10)

4(16)

2(5)

7(18)

3(19

)6(9)

7(10)

2(15)

3(7)

6(15)

C71

(68)

31(62)

04702

58(71)

50(63)

040

7518

(56)

90(69)

02089

89(66)

18(69)

0458

58(69)

50(64)

05103

T33

(32)

19(38)

24(29)

30(38)

14(44)

40(31)

45(34)

8(31)

26(31)

28(36)


Table5Com

paris

onof

geno

type

andallelefre

quencies

ofglucocortic

oidmetabolism

gene

varia

ntsandselected

clinicalfeaturesGC

glucocorticoidmedication

NR

norespon

seIS

immun

osup

pressiv

edrugs119901

values

lower

than

005

arem

arkedwithlowast

Gene

SNP

Genotype

Relap

ses

Frequent

relap

ser()

Age

ofon

set()

Respon

seto

GC

Treatm

ent

lt5gt5

119901No

Yes

119901lt3gt3

119901Normal

Slow

NR119901

OnlyGCs

IS119901

119899=52119899=25

119899=41119899=40

119899=16119899=65

119899=67119899=13

119899=42119899=39

MDR1

rs1128503

(c12

36Cgt

T)

CC12

(23)

4(16)

02330

9(22)

8(20)

04526

1(6)

16(25)

02863

14(21)

3(23)

1000

12(29)

5(17)

001lowast

CT29

(56)

11(44)

23(56)

18(45)

10(63)

31(48)

34(51)

6(46)

24(57)

7(24)

TT11(21)

10(40)

9(22)

14(35)

5(31)

18(28)

19(28)

4(31)

6(14

)17

(59)

C53

(51)

19(38)

01678

41(50)

34(43)

03496

12(38)

63(48)

03240

62(46)

12(46)

00566

48(57)

17(29)

000

12lowast

T51

(49)

31(62)

41(50)

46(58)

20(63)

67(52)

72(54)

14(54)

36(43)

41(71)

rs2032582

(c2677GgtTA)

GG

9(17)

4(16)

05655

6(15)

7(185)

03793

1(6)

12(18)

03311

12(18)

1(8)

04136

10(24)

3(8)

000

67lowast

GT

25(48)

11(44)

22(54)

17(435)

7(44)

32(49)

32(48)

6(46)

22(53)

17(44)

TT13

(25)

10(40)

9(22)

15(385)

7(44)

17(26)

20(30)

4(31)

6(14

)18

(46)

TA2(4)

0(0)

2(5)

0(0)

1(6)

1(2)

1(1)

1(8)

2(5)

0(0)

GA

3(6)

0(0)

2(5)

1(35)

03(5)

2(3)

1(8)

2(5)

1(3)

G46

(44)

19(38)

01985

36(44)

32(40)

03448

9(28)

59(45)

01642

58(43)

9(35)

00529

44(52)

24(31)

000

28lowast

T53

(51)

31(62)

42(51)

47(59)

22(69)

67(52)

73(54)

15(58)

36(43)

53(68)

A5(6)

0(0)

4(5)

1(1)

1(3)

4(3)

3(3)

2(8)

4(5)

1(1)

rs104564

2(c3435CgtT)

CC9(17)

4(16)

1000

8(20)

5(12)

04179

0(0)

13(20)

003

15lowast

12(18)

1(8)

08447

10(24)

3(8)

003

89lowast

CT23

(44)

11(44)

19(46)

16(39)

11(69)

24(37)

28(42)

6(46)

20(48)

15(38)

TT20

(38)

10(40)

14(34)

19(46)

5(31)

28(43)

27(40)

6(46)

12(29)

21(54)

C41

(39)

19(38)

1000

35(43)

26(33)

11977

11(34)

50(38)

08389

52(39)

8(31)

001

13lowast

40(48)

21(27)

000

92lowast

T63

(61)

31(62)

47(57)

54(68)

21(66)

80(62)

82(61)

18(69)

44(52)

57(73)

GLCC

I1

rs37972(c-1473TgtC)

CC16

(31)

11(44)

04931

13(32)

15(38)

08291

8(50)

20(31)

02289

24(36)

4(31)

1000

11(26)

17(44)

02726

CT26

(50)

11(44)

21(51)

20(50)

5(31)

35(54)

33(49)

7(54)

23(55)

17(44)

TT10

(19)

3(12)

7(17)

5(13)

3(19

)10

(15)

10(15)

2(15)

8(19

)5(13)

C58

(56)

33(66)

02938

47(57)

50(63)

0525

21(66)

75(58)

05473

81(60)

15(58)

1000

45(54)

51(65)

01506

T46

(44)

17(34)

35(43)

30(38)

11(34)

55(42)

53(40)

11(42)

39(46)

27(35)

rs37973(c-1106GgtA)

AA

14(27)

12(48)

0119

712

(29)

15(38)

06024

8(50)

19(29)

01861

22(33)

5(38)

08423

9(21)

18846)

00623

GA

26(50)

11(44)

21(51)

20(50)

5(31)

35(54)

33(49)

7(54)

24(57)

16(41)

GG

12(23)

2(8)

8(20)

5(13

3(19

)11(17)

12(18)

1(8)

9(21)

5(13)

A54

(52)

35(70)

003

77lowast

45(55)

50(63)

03427

21(66)

73(56)

04246

77(57)

17(65)

06321

42(50)

52(67)

00387

G50

(48)

15(30)

37(45)

30(38)

11(34)

57(44)

57(43)

9(35)

42(50)

26(33)

NR3

C1rs41423247

(c1184+6

46Cgt

G)

GG

20(38)

5(20)

001

73lowast

14(34)

11(28)

004

42lowast

5(31)

21(32)

05928

23(34)

2(15)

02363

16(38)

10(26)

00655

GC

17(33)

17(68)

14(34)

24(60)

6(38)

31(48)

31(46)

6(46)

14(33)

23(59)

CC15

(29)

3(12)

13(32)

5(13)

5(31)

13(20)

13(19

)5(38)

12(29)

6(15)

G57

(55)

27(54)

1000

42(51)

46(58)

04352

16(50)

73(56)

05571

77(57)

10(38)

03479

46(55)

43(55)

1000

C47

(45)

23(46)

40(49)

34(43)

16(50)

57(44)

57(43)

16(62)

38(45)

35(45)


Table 6 Comparison of haplotype distributions of the MDR1 loci in patients and controls as well as in patients with less than 5 relapses andpatients with five or more relapses Variants in order rs1128503 rs2032582 and rs1045642 119901 values lower than 005 are marked with lowast

Haplotype Patients (119899 = 82) Controls (119899 = 98) OR (95 CI) 119901119873 119873

CTC 69 422 46 234 042 (027ndash066) 0002TGT 45 275 36 186 060 (036ndash098) 00412TTC 13 81 31 156 218 (110ndash433) 00254CGC 7 45 25 126 328 (138ndash779) 00072TGC 11 65 20 100 158 (073ndash340) 0242CGT 7 42 15 78 186 (074ndash467) 01877TTT 2 13 15 77 671 (151ndash2980) 00123Other 9 57 8 43 073 (028ndash194) 05425

Haplotype Relapses lt5 (119899 = 52) Relapses gt5 (119899 = 25) OR (95 CI) 119901119873 119873

CTC 42 406 28 553 188 (095ndash371) 007TGT 32 304 16 314 106 (051ndash291) 088TGC 10 95 1 24 019 (002ndash154) 01205TTC 6 62 2 42 068 (013ndash350) 064CGT 2 20 2 40 213 (029ndash1554) 04578CTT 3 32 1 26 069 (007ndash678) 07479Other 8 81 0 00 011 (001ndash199) 01359

response time Similar associationwas observed by Choi et al[22] and Youssef et al [12] although interestingly the majorhaplotype linked with this property varies between studiesOur study did not find this association and Cizmarikovaet al [30] reached similar conclusion The two major hap-lotypes found in our study were TTT and CGC Thesetwo were predominant in patient samples with combinedallele frequency of 70 The remaining 30 was distributedbetween eight other haplotypes none of them reaching 10frequency In control patients TTT and CGC were also themost common haplotypes but the distribution was morediverse as five haplotypes had higher than 10 frequencyPrevious studies have also shown that TTT and CGC areprevalent haplotypes both in patients and in control subjects[9 12 22 30] Interestingly Choi et al [22] and Youssef etal [12] found haplotype TGC to have a frequency equal toTTT andCGC and have association to steroid responsivenesswhile Cizmarikova et al [30] found the frequency of TGCto be under 3 in patients and in controls and have noassociation to any clinical attribute Our results are similarto the latter study as TGC frequency reaches just 10 incontrol samples and 65 in patients It is possible that thedifferences are caused by haplotype frequency differencesbetween populations

NR3C1 codes for glucocorticoid receptor (GR) that canaffect the regulation of many biological functions includingresponsiveness to GC and its functional variability may playa role in the therapeutic response to GC In this study weanalyzed NR3C1 SNP rs41423247 and curiously found thatpatients with more than five relapses carried more frequently

heterozygous GC genotype than those with less than fiverelapses (68 versus 33) The amount of both CC and GGhomozygotes was diminished in these frequent relapsersThe allele distribution between groups with over and underfive relapses showed no difference In some previous studiesG allele (especially as a part of the intron B three-SNPhaplotype) has been associated with increased GC sensitivity[31 32] while others could not confirm the association [14]It is still unclear how our findings fit in with these studiesSimilar increased portion of heterozygous genotype was seenin patients with severe course of the disease compared tothose with milder course (63 versus 34)

An interesting new gene in the context of INS is GLCCI1Tantisira et al [33] first showed that SNPs rs37973 andrs37972 which are in linkage disequilibrium associated withpoor responsiveness to GCs in asthmatic patients Soonafterwards Nishibori et al [15] showed that Glcci1-protein ishighly expressed in glomerular podocytes and its deficiencyleads to proteinuria Based on these findings Cheong etal [16] looked to see if these SNPs were playing a role inGC responsiveness in NS but could find no associationSimilarly our results show no direct association between thealleles andor genotypes of either SNP or GC responsivenessHowever while rs37972 showed no significant associationwith any clinical feature the frequency of the rs37973 A allelewas higher in patients with more than five relapses (70 versus52) and in patientswho received IS drugs compared to thosewho received only GC medication (67 versus 50) To ourknowledge this association has not been looked into in otherstudies


Table 7 Comparison between the found associations of the analyzed SNPs in this study and in previous studies

Gene Found association Current study Referenced study

GPC5

rs16946160 (c325+1026376GgtA)Association of AA genotype with NS No Yes [7]Association of A allele with disease onset YesA allele frequency 0168 008 [7]

IL13 rs848 (clowast526CgtA)Association of genotype distribution with long term outcome No Yes [4]

MIFrs755622 (c-270GgtC)Association of C allele andor GC genotype with NS No Yes [5] yes [6] no [22]Association of CC genotype with GC resistance No Yes [5] yes [6] no [22]

nNOSrs2662826 (clowast276CgtT)Association of TT genotype with NS No Yes [8]Association of TT genotype with GC responsiveness No No [8]

MDR1

rs1128503 (c1236CgtT)Association of T allele andor TT genotypes with IS medication need Yesrs2032582 (c2677GgtTA)

Association of genotype distribution with NS No No [9] yes [11] yes [12] no[22]

Association of CC genotype with age of onset No No [9] no [11] yes [12] no[22]

Association of T allele andor TT genotype with GC responsiveness YesAssociation of T allele andor TT genotypes with IS medication need Yesrs1045642 (c3435CgtT)

Association of T allele andor TT genotype with NS No Yes [9] yes [11] yes [12] no[22]

Allele frequencies of controls (CT ) 372628452548 [9] 664336 [11]585415 [12] 420580[22] 424576 [30]

Association of CC genotype with age of onset Yes No [9] no [11] yes [12] no[22]

Association of T allele andor TT genotypes with IS medication need YesHaplo type

Association with GC responsiveness No Yes [9] yes [12] yes [22] no[30]

Frequency of TGC haplotype (casecontrol ) 65201011lowast [9] 8365 [11]

217186 [12] 21218 [22]1123 [30]

GLCCI1

rs37972 (c-1473TgtC)Association of genotype distribution with GC responsiveness No No [16]rs37973 (c-1106GgtA)Association of genotype distribution with GC responsiveness No No [16]Association of A allele with patients with more than five relapses YesAssociation of A allele with IS medication need Yes

lowastOnly control

5 Conclusion

The studied genetic variants have little role in the course ofNS in Finnish patients A notable exception to this is MDR1SNPs whose genotype and allele distribution show significantassociation to different medication regimes The genetic

background to GC sensitivity is very heterogenic and variesbetween ethnic groups which may have to be consideredwhen drawing up treatment strategies for individual patientsMore work needs to be done to discover other contributingmolecules before the genetics of steroid responsiveness in NScan be understood


Competing Interests

The authors declare that there is no conflict of interestsregarding the publication of this paper

References

[1] L C Clement C Avila-Casado C Mace et al ldquoPodocyte-secreted angiopoietin-like-4 mediates proteinuria in gluco-corticoid-sensitive nephrotic syndromerdquo Nature Medicine vol17 no 1 pp 117ndash122 2011

[2] L C Clement C Mace C Avila-Casado J A Joles S Kerstenand S S Chugh ldquoCirculating angiopoietin-like 4 links protein-uria with hypertriglyceridemia in nephrotic syndromerdquo NatureMedicine vol 20 no 1 pp 37ndash46 2014

[3] B Acharya T Shirakawa A Pungky et al ldquoPolymorphismof the interleukin-4 interleukin-13 and signal transducer andactivator of transcription 6 genes in Indonesian children withminimal change nephrotic syndromerdquo American Journal ofNephrology vol 25 no 1 pp 30ndash35 2005

[4] C-LWeiW Cheung C-K Heng et al ldquoInterleukin-13 geneticpolymorphisms in Singapore Chinese children correlate withlong-term outcome of minimal-change diseaserdquo NephrologyDialysis Transplantation vol 20 no 4 pp 728ndash734 2005

[5] A Berdeli S Mir N Ozkayin E Serdaroglu Y Tabel and ACura ldquoAssociation of macrophage migration inhibitory factor-173C allele polymorphism with steroid resistance in childrenwith nephrotic syndromerdquo Pediatric Nephrology vol 20 no 11pp 1566ndash1571 2005

[6] M Vivarelli L E DrsquoUrbano G Stringini et al ldquoAssociation ofthe macrophage migration inhibitory factor -173lowastC allele withchildhood nephrotic syndromerdquo Pediatric Nephrology vol 23no 5 pp 743ndash748 2008

[7] K Okamoto K Tokunaga K Doi et al ldquoCommon variation inGPC5 is associated with acquired nephrotic syndromerdquo NatureGenetics vol 43 no 5 pp 459ndash463 2011

[8] B Alasehirli A Balat O Barlas and A Kont ldquoNitric oxidesynthase gene polymorphisms in children withminimal changenephrotic syndromerdquo Pediatrics International vol 51 no 1 pp75ndash78 2009

[9] A Wasilewska G Zalewski L Chyczewski and W Zoch-Zwierz ldquoMDR-1 gene polymorphisms and clinical course ofsteroid-responsive nephrotic syndrome in childrenrdquo PediatricNephrology vol 22 no 1 pp 44ndash51 2007

[10] S Funaki S Takahashi NWada HMurakami and K HaradaldquoMultiple drug-resistant gene 1 in children with steroid-sen-sitive nephrotic syndromerdquo Pediatrics International vol 50 no2 pp 159ndash161 2008

[11] T Jafar N Prasad V Agarwal et al ldquoMDR-1 gene polymor-phisms in steroid-responsive versus steroid-resistant nephroticsyndrome in childrenrdquoNephrologyDialysis Transplantation vol26 no 12 pp 3968ndash3974 2011

[12] DM Youssef T A Attia A S El-Shal and F A AbduelomettyldquoMulti-drug resistance-1 gene polymorphisms in nephroticsyndrome impact on susceptibility and response to steroidsrdquoGene vol 530 no 2 pp 201ndash207 2013

[13] J Ye Z Yu J Ding et al ldquoGenetic variations of the NR3C1 genein children with sporadic nephrotic syndromerdquo Biochemicaland Biophysical Research Communications vol 348 no 2 pp507ndash513 2006

[14] N Teeninga J E Kist-van Holthe E L T van den Akker et alldquoGenetic and in vivo determinants of glucocorticoid sensitivity

in relation to clinical outcome of childhood nephrotic syn-dromerdquoKidney International vol 85 no 6 pp 1444ndash1453 2014

[15] Y Nishibori K Katayama M Parikka et al ldquoGlcci1 deficiencyleads to proteinuriardquo Journal of the American Society of Nephrol-ogy vol 22 no 11 pp 2037ndash2046 2011

[16] H I Cheong H G Kang and J Schlondorff ldquoGLCCI1 singlenucleotide polymorphisms in pediatric nephrotic syndromerdquoPediatric Nephrology vol 27 no 9 pp 1595ndash1599 2012

[17] A-T Lahdenkari M Suvanto E Kajantie O Koskimies MKestila and H Jalanko ldquoClinical features and outcome ofchildhood minimal change nephrotic syndrome is geneticsinvolvedrdquo Pediatric Nephrology vol 20 no 8 pp 1073ndash10802005

[18] U Lenkkeri M Mannikko P McCready et al ldquoStructure ofthe gene for congenital nephrotic syndrome of the finnishtype (NPHS1) and characterization ofmutationsrdquoTheAmericanJournal of Human Genetics vol 64 no 1 pp 51ndash61 1999

[19] M Stephens N J Smith and P Donnelly ldquoA new statisticalmethod for haplotype reconstruction from population datardquoAmerican Journal of Human Genetics vol 68 no 4 pp 978ndash989 2001

[20] M Stephens and P Scheet ldquoAccounting for decay of linkagedisequilibrium in haplotype inference and missing-data impu-tationrdquo American Journal of Human Genetics vol 76 no 3 pp449ndash462 2005

[21] N E Buroker X-HNing Z-N Zhou et al ldquoAKT3 ANGPTL4eNOS3 and VEGFA associations with high altitude sicknessin Han and Tibetan Chinese at the Qinghai-Tibetan plateaurdquoInternational Journal of Hematology vol 96 no 2 pp 200ndash2132012

[22] H J Choi H Y Cho H Ro et al ldquoPolymorphisms of theMDR1and MIF genes in children with nephrotic syndromerdquo PediatricNephrology vol 26 no 11 pp 1981ndash1988 2011

[23] I Fleury P BeaulieuM Primeau D Labuda D Sinnett andMKrajinovic ldquoCharacterization of the BclI polymorphism in theglucocorticoid receptor generdquo Clinical Chemistry vol 49 no 9pp 1528ndash1531 2003

[24] K Yoshida T Shimizugawa M Ono and H FurukawaldquoAngiopoietin-like protein 4 is a potent hyperlipidemia-inducing factor in mice and inhibitor of lipoprotein lipaserdquoJournal of Lipid Research vol 43 no 11 pp 1770ndash1772 2002

[25] S S Chugh L C Clement and C Mace ldquoNew insights intohuman minimal change disease lessons from animal modelsrdquoAmerican Journal of Kidney Diseases vol 59 no 2 pp 284ndash2922012

[26] M C Smart-Halajko M R Robciuc J A Cooper et alldquoThe relationship between plasma angiopoietin-like protein 4levels angiopoietin-like protein 4 genotype and coronary heartdisease riskrdquo Arteriosclerosis Thrombosis and Vascular Biologyvol 30 no 11 pp 2277ndash2282 2010

[27] R B Kim B F Leake E F Choo et al ldquoIdentification of func-tionally variant MDR1 alleles among European Americans andAfrican Americansrdquo Clinical Pharmacology and Therapeuticsvol 70 no 2 pp 189ndash199 2001

[28] D Anglicheau M Flamant M H Schlageter et al ldquoPharma-cokinetic interaction between corticosteroids and tacrolimusafter renal transplantationrdquo Nephrology Dialysis Transplanta-tion vol 18 no 11 pp 2409ndash2414 2003

[29] M-M Ameyaw F Regateiro T Li et al ldquoMDR1 pharma-cogenetics frequency of the C3435T mutation in exon 26 issignificantly influenced by ethnicityrdquo Pharmacogenetics vol 11no 3 pp 217ndash221 2001


[30] M Cizmarikova L Podracka L Klimcakova et al ldquoMDR1polymorphisms and idiopathic nephrotic syndrome in Slovakchildren preliminary resultsrdquo Medical Science Monitor vol 21pp 59Sndash68S 2015

[31] E F C van Rossum and S W J Lamberts ldquoPolymorphismsin the glucocorticoid receptor gene and their associations withmetabolic parameters and body compositionrdquo Recent Progressin Hormone Research vol 59 pp 333ndash357 2004

[32] G Zalewski A Wasilewska W Zoch-Zwierz and L Chy-czewski ldquoResponse to prednisone in relation to NR3C1 intronB polymorphisms in childhood nephrotic syndromerdquo PediatricNephrology vol 23 no 7 pp 1073ndash1078 2008

[33] K G Tantisira J Lasky-Su M Harada et al ldquoGenomewideassociation between GLCCI1 and response to glucocorticoidtherapy in asthmardquo The New England Journal of Medicine vol365 no 13 pp 1173ndash1183 2011

Submit your manuscripts athttpwwwhindawicom

Stem CellsInternational

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014


MEDIATORSINFLAMMATION

of


Behavioural Neurology

EndocrinologyInternational Journal of



Disease Markers


BioMed Research International

OncologyJournal of



Oxidative Medicine and Cellular Longevity


PPAR Research

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

ObesityJournal of



Computational and Mathematical Methods in Medicine

OphthalmologyJournal of


Diabetes ResearchJournal of



Research and TreatmentAIDS


Gastroenterology Research and Practice


Parkinsonrsquos Disease

Evidence-Based Complementary and Alternative Medicine

Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom


Table 1 Primer sequences 119879119898 annealing temperature

Gene SNP Forward 51015840-31015840 Reverse 51015840-31015840 119879119898(∘C)

Angptl4 rs1044250 (c797CgtT) CTACAAGGCGGGGTTTGGGGAT AAGTGGAGAAGGGTACGGAGAGGCC 62

GPC5 rs16946160(c325+1026376GgtA) AGAGTTGACAAGAGTTAAACAGCA GTCATCTCTGACTCCGCAGTAT 58

IL-13 rs848 (clowast526CgtA) GTTTGTCACCGTTGGGGATTGG CAATGTCCCCTCCCCCAGTGTT 62MIF rs755622 (c-270GgtC) CTAAGAAAGACCCGAGGCGA GGCACGTTGGTGTTTACGAT 58nNOS rs2662826 (clowast276CgtT) ACTCCTTGAGTTTTCCTGCTGCGA CCATGTTCCAGTGGTTTCATGCACCC 62

MDR1

rs1128503 (c1236CgtT) TATCCTGTGTCTGTGAATTGCC CTGACTCACCACACCAATG 62rs2032582

(c2677GgtTA) TGCAGGCTATAGGTTCCAGG TTTAGTTTGACTCACCTTCCCG 60

rs1045642 (c3435CgtT) TGTTTTCAGCTGCTTGATGG AAGGCATGTATGTTGGCCTC 58

GLCCI1rs37972 (c-1473TgtC) GACCCCTGCATATAGTGCCT AATGAAACTGAAAGCGTACAAAGA 58rs37973 (c-1106GgtA) AATTCCTTGTTGACCCCTGC AGCTGAGTTTTCGTGACCAG 62

NR3C1 rs41423247(c1184+646CgtG) AAATTGAAGCTTAACAATTTTGGC GCAGTGAACAGTGTACCAGACC 58

(GLCCI1) that encodes Glcci1 protein that associated withglucocorticoid (GC) responsiveness and development ofproteinuria in animal models [15 16]

In this study we genotyped eleven single nucleotide poly-morphisms (SNPs) from the above mentioned eight genesfrom DNA samples obtained from a unique cohort of INSpatients followed up over 30 years The results show that thevariants in the genes coding for functional kidney proteinshave little clinical relevance in INS while variants in genesinvolved in glucocorticoid metabolism show marginal asso-ciation with INS The genotype distribution of MDR1 SNPsshows significant association with medication regime as theminor alleles of the SNPs are more frequent in patients whoreceive immunosuppressive medication in addition to gluco-corticoids

2 Materials and Methods

21 Patients The study cohort included 100 INS patients ofwhom 83were diagnosed within 1965ndash1981 at theHospital forChildren and Adolescents University of Helsinki These 83patients were enrolled in the International Study of KidneyDisease in Children (ISKDC) and were treated by protocolsstill used in pediatric nephrology The mean age at the lastfollow-up was 350 years (range 251ndash441 years) Clinical datawere carefully recorded from the patient records as was pre-viously reported in detail [17]The remaining 17 patients werediagnosed more recently at the Hospital for Children andAdolescents University of Helsinki and were still children oradolescents of them SNP genotypes were used in statisticalcomparison between INS patients and controls A bloodsample for DNA extraction was gathered from all

The controls included a cohort of 101 subjects who wereeither healthy adults or suffered from nonkidney relatedcondition

22 SNPs and PCR Analysis We selected eleven SNPsfrom eight genes to this study based on previous reportsin literature on their association with INS The genes and

SNPs were Angptl4 SNP rs1044250 (c797CgtT) GPC5SNP rs16946160 (c325+102637GgtA) IL-13 SNP rs848(clowast526CgtA) MIF rs755622 (c-270GgtC) nNOS rs2682826(clowast276CgtT)MDR1 SNPs rs1128503 (c1236CgtT) rs2032582(c2677GgtTA) rs1045642 (c3435CgtT) GLCC11 SNPsrs37972 (c-1473CgtT) and rs37973 (c-1106AgtG) and NR3C1rs41423247 (c1184+646GgtC) Analysis was carried out usingdirect sequencing Exons were amplified by PCR withflanking intronic primers and the reactions were performedin total volumes of 25120583L as previously described [18]Occasionally the denaturation temperature was raised upto 98∘C or betaine was added to the reaction mixturePCR products were genotyped using automated sequenceanalysis by BigDye-terminator chemistry (v31) on GeneticAnalyzer 3730 (Applied Biosystems) The sequences wereanalyzed with GeneComposer version 1101051 (httpwwwGeneComposercom) The genotypes were comparedbetween patients and controls and among various clinicalvariables that include age of onset (lt3 yr versus gt3 yr)number of relapses (lt5 versus gt5) frequent relapses(no versus yes) response to GC (normal versus slownoresponse) treatment (only GC versus GC together withimmunosuppressive (IS) drugs) and GC dependence (noversus yes)

The genotypes of the threeMDR1 variants (rs1236 rs2677and rs3435) were used to carry out a haplotype analysisTwelve haplotypes were derived from the genotype data usingthe program PHASE (v21) [19 20] The estimated MDR1haplotype frequencies were compared between patients andcontrols and among various clinical variables

All primers are presented in Table 1 Most of the primersequences are gathered from literature Angptl4 rs1044250[21] IL-13 rs848 [4] MIF rs755622 [22] nNOS rs2682826[8] MDR1 rs1128503 rs2032582 rs1045642 [9] and NR3C1rs41423247 [23] Primers for GLCC11 (NM 138426) rs37972and rs37973 and GPC5 (NM 004466) rs16946160 weredesigned using primer3 program (httpwwwncbinlmnihgovtoolsprimer-blast)




3 Results








4 Discussion







2


119901


GPC5 rs16946160(c325+1026376GgtA)

GG 88 884 041 gt005 86 856 025 gt005GA 12 113 14 147AA 0 04 1 06




MDR1


rs2032582(c2677GgtTA)



GLCCI1



NR3C1 rs41423247(c1184+646CgtG)

GG 32 308 024 gt005 37 342 153 gt005GC 47 494 37 426CC 21 198 16 132







119899 = 100 119899 = 84



119899 = 100 119899 = 101

GPC5 rs16946160(c325+1026376GgtA)



119899 = 100 119899 = 101




119899 = 100 119899 = 101



119899 = 100 119899 = 99



119899 = 100 119899 = 98

MDR1

rs1128503(c1236CgtT)


119899 = 100 119899 = 98

rs2032582(c2677GgtTA)


119899 = 100 119899 = 98

rs1045642(c3435CgtT)



Table 3 Continued


119899 = 100 119899 = 97

GLCCI1

rs37972 (c-1473TgtC)


119899 = 100 119899 = 90

rs37973 (c-1106GgtA)


119899 = 100 119899 = 90

NR3C1 rs41423247(c1184+646CgtG)









Table4Com

paris

onof

geno

type

andallelefre

quencies

offunctio

nalkidneygene

varia

ntsa

ndselected


lower

than

005

arem

arkedwithlowast

Gene

SNP

Genotype

Relap

ses

Frequent

relap

ser()

Age

ofon

set()

Respon

seto

steroids

Treatm

ent

lt5

gt5119901

No

Yes119901

lt3gt3

119901Normal

Slow

NR119901

OnlyGC

IS119901

119899=52119899=25

119899=41119899=40

119899=16119899=65

119899=67119899=13

119899=42119899=39

Angptl4

rs1044

250(c797Cgt

T)

CC20

(38)

11(44)

09426

14(34)

18(44)

04133

8(50)

24(37)

03311

25(37)

6(46)

08494

12(29)

20(51)

00679

CT25

(48)

11(44)

19(46)

18(44)

6(38)

31(48)

32(48)

5(38)

21(50)

16(41)

TT7(13)

3(12)

8(20)

4(10)

2(13)

10(15)

10(15)

2(15)

9(21)

3(8)

C65

(625)

33(66)

07230

47(57)

54(68)

01977

22(69)

79(61)

05416

82(61)

17(65)

08094

45(54)

56(72)

002

28lowast

T39

(375

)17

(34)

35(43)

26(33)

10(31)

51(39)

52(39)

9(35)

39(46)

22(28)

GPC

5rs16946160

(c32

5+1026376GgtA)

GG

47(90)

20(80)

02789

37(90)

33(83)

03493

11(69)

59(91)

00359lowast

58(87)

11(85)

1000

38(90)

32(82)

03389

GA

5(10)

5(20)

4(10)

7(18)

5(31)

6(9)

9(13)

2(15)

4(10)

7(18)

AA

0(0)

0(0)

0(0)

0(0)

0(0)

0(0)

0(0)

0(0)

0(0)

0(0)

G99

(95)

45(90)

02951

78(95)

73(91)

03663

27(84)

124(95)

00421lowast

125(93)

24(92)

06322

80(95)

71(91)

03567

A5(5)

5(10)

4(5)

7(9)

5(16)

6(5)

9(7)

2(8)

4(5)

7(9)

IL13


CC18

(35)

8(32)

08456

10(24)

16(40)

03114

7(44)

19(29)

064

2024

(36)

2(15)

03703

15(36)

11(28)

07568

CA25

(48)

14(56)

24(59)

19(48)

7(44)

35(54)

33(49)

9(69)

21(50)

21(54)

AA

9(17)

3(12)

7(17)

5(13)

2(13)

11(17)

10(15)

2(15)

6(14

)7(18)

C61

(59)

30(60)

1000

44(54)

51(64)

02056

21(66)

73(56)

04246

81(60)

13(50)

1000

51(61)

43(55)

05253

A43

(41)

20(40)

38(46)

29(36)

11(34)

57(44)

53(40)

13(50)

33(39)

35(45)

MIF

rs755622

(c-2

70GgtC)

GG

31(60)

16(64)

1000

26(63)

24(60)

09284

9(56)

40(62)

00634

40(60)

8(62)

1000

25(60)

24(62)

07481

GC

18(35)

8(32)

13(32)

14(35)

7(44)

21(32)

23(34)

5(38)

14(33)

14(36)

CC3(6)

1(4)

2(5)

2(5)

0(0)

4(6)

4(6)

0(0)

3(7)

1(3)

G80

(77)

40(80)

08359

65(79)

62(78)

08497

25(78)

101(78)

1000

103(77)

21(81)

1000

64(76)

62(79)

07063

C24

(23)

10(20)

17(21)

18(23)

7(22)

29(22)

31(23)

5(19)

20(24)

16(21)

nNOS

rs2662826

(clowast276CgtT)

CC24

(46)

10(4)

07393

19(46)

17(43)

02027

5(31)

31(48)

040

8029

(43)

7(54)

06178

19(45)

17(44)

05406

CT23

(44)

11(44)

20(49)

16(40

8(50)

28(43)

31(46)

4(31)

20(48)

16(41)

TT5(10)

4(16)

2(5)

7(18)

3(19

)6(9)

7(10)

2(15)

3(7)

6(15)

C71

(68)

31(62)

04702

58(71)

50(63)

040

7518

(56)

90(69)

02089

89(66)

18(69)

0458

58(69)

50(64)

05103

T33

(32)

19(38)

24(29)

30(38)

14(44)

40(31)

45(34)

8(31)

26(31)

28(36)


Table5Com

paris

onof

geno

type

andallelefre

quencies

ofglucocortic

oidmetabolism

gene

varia

ntsandselected

clinicalfeaturesGC


NR

norespon

seIS

immun

osup

pressiv

edrugs119901

values

lower

than

005

arem

arkedwithlowast

Gene

SNP

Genotype

Relap

ses

Frequent

relap

ser()

Age

ofon

set()

Respon

seto

GC

Treatm

ent

lt5gt5

119901No

Yes

119901lt3gt3

119901Normal

Slow

NR119901

OnlyGCs

IS119901

119899=52119899=25

119899=41119899=40

119899=16119899=65

119899=67119899=13

119899=42119899=39

MDR1

rs1128503

(c12

36Cgt

T)

CC12

(23)

4(16)

02330

9(22)

8(20)

04526

1(6)

16(25)

02863

14(21)

3(23)

1000

12(29)

5(17)

001lowast

CT29

(56)

11(44)

23(56)

18(45)

10(63)

31(48)

34(51)

6(46)

24(57)

7(24)

TT11(21)

10(40)

9(22)

14(35)

5(31)

18(28)

19(28)

4(31)

6(14

)17

(59)

C53

(51)

19(38)

01678

41(50)

34(43)

03496

12(38)

63(48)

03240

62(46)

12(46)

00566

48(57)

17(29)

000

12lowast

T51

(49)

31(62)

41(50)

46(58)

20(63)

67(52)

72(54)

14(54)

36(43)

41(71)

rs2032582

(c2677GgtTA)

GG

9(17)

4(16)

05655

6(15)

7(185)

03793

1(6)

12(18)

03311

12(18)

1(8)

04136

10(24)

3(8)

000

67lowast

GT

25(48)

11(44)

22(54)

17(435)

7(44)

32(49)

32(48)

6(46)

22(53)

17(44)

TT13

(25)

10(40)

9(22)

15(385)

7(44)

17(26)

20(30)

4(31)

6(14

)18

(46)

TA2(4)

0(0)

2(5)

0(0)

1(6)

1(2)

1(1)

1(8)

2(5)

0(0)

GA

3(6)

0(0)

2(5)

1(35)

03(5)

2(3)

1(8)

2(5)

1(3)

G46

(44)

19(38)

01985

36(44)

32(40)

03448

9(28)

59(45)

01642

58(43)

9(35)

00529

44(52)

24(31)

000

28lowast

T53

(51)

31(62)

42(51)

47(59)

22(69)

67(52)

73(54)

15(58)

36(43)

53(68)

A5(6)

0(0)

4(5)

1(1)

1(3)

4(3)

3(3)

2(8)

4(5)

1(1)

rs104564

2(c3435CgtT)

CC9(17)

4(16)

1000

8(20)

5(12)

04179

0(0)

13(20)

003

15lowast

12(18)

1(8)

08447

10(24)

3(8)

003

89lowast

CT23

(44)

11(44)

19(46)

16(39)

11(69)

24(37)

28(42)

6(46)

20(48)

15(38)

TT20

(38)

10(40)

14(34)

19(46)

5(31)

28(43)

27(40)

6(46)

12(29)

21(54)

C41

(39)

19(38)

1000

35(43)

26(33)

11977

11(34)

50(38)

08389

52(39)

8(31)

001

13lowast

40(48)

21(27)

000

92lowast

T63

(61)

31(62)

47(57)

54(68)

21(66)

80(62)

82(61)

18(69)

44(52)

57(73)

GLCC

I1

rs37972(c-1473TgtC)

CC16

(31)

11(44)

04931

13(32)

15(38)

08291

8(50)

20(31)

02289

24(36)

4(31)

1000

11(26)

17(44)

02726

CT26

(50)

11(44)

21(51)

20(50)

5(31)

35(54)

33(49)

7(54)

23(55)

17(44)

TT10

(19)

3(12)

7(17)

5(13)

3(19

)10

(15)

10(15)

2(15)

8(19

)5(13)

C58

(56)

33(66)

02938

47(57)

50(63)

0525

21(66)

75(58)

05473

81(60)

15(58)

1000

45(54)

51(65)

01506

T46

(44)

17(34)

35(43)

30(38)

11(34)

55(42)

53(40)

11(42)

39(46)

27(35)

rs37973(c-1106GgtA)

AA

14(27)

12(48)

0119

712

(29)

15(38)

06024

8(50)

19(29)

01861

22(33)

5(38)

08423

9(21)

18846)

00623

GA

26(50)

11(44)

21(51)

20(50)

5(31)

35(54)

33(49)

7(54)

24(57)

16(41)

GG

12(23)

2(8)

8(20)

5(13

3(19

)11(17)

12(18)

1(8)

9(21)

5(13)

A54

(52)

35(70)

003

77lowast

45(55)

50(63)

03427

21(66)

73(56)

04246

77(57)

17(65)

06321

42(50)

52(67)

00387

G50

(48)

15(30)

37(45)

30(38)

11(34)

57(44)

57(43)

9(35)

42(50)

26(33)

NR3

C1rs41423247

(c1184+6

46Cgt

G)

GG

20(38)

5(20)

001

73lowast

14(34)

11(28)

004

42lowast

5(31)

21(32)

05928

23(34)

2(15)

02363

16(38)

10(26)

00655

GC

17(33)

17(68)

14(34)

24(60)

6(38)

31(48)

31(46)

6(46)

14(33)

23(59)

CC15

(29)

3(12)

13(32)

5(13)

5(31)

13(20)

13(19

)5(38)

12(29)

6(15)

G57

(55)

27(54)

1000

42(51)

46(58)

04352

16(50)

73(56)

05571

77(57)

10(38)

03479

46(55)

43(55)

1000

C47

(45)

23(46)

40(49)

34(43)

16(50)

57(44)

57(43)

16(62)

38(45)

35(45)














GPC5





MDR1











217186 [12] 21218 [22]1123 [30]

GLCCI1


lowastOnly control

5 Conclusion




Competing Interests


References









































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of



















3 Results








4 Discussion







2


119901


GPC5 rs16946160(c325+1026376GgtA)

GG 88 884 041 gt005 86 856 025 gt005GA 12 113 14 147AA 0 04 1 06




MDR1


rs2032582(c2677GgtTA)



GLCCI1



NR3C1 rs41423247(c1184+646CgtG)

GG 32 308 024 gt005 37 342 153 gt005GC 47 494 37 426CC 21 198 16 132







119899 = 100 119899 = 84



119899 = 100 119899 = 101

GPC5 rs16946160(c325+1026376GgtA)



119899 = 100 119899 = 101




119899 = 100 119899 = 101



119899 = 100 119899 = 99



119899 = 100 119899 = 98

MDR1

rs1128503(c1236CgtT)


119899 = 100 119899 = 98

rs2032582(c2677GgtTA)


119899 = 100 119899 = 98

rs1045642(c3435CgtT)



Table 3 Continued


119899 = 100 119899 = 97

GLCCI1

rs37972 (c-1473TgtC)


119899 = 100 119899 = 90

rs37973 (c-1106GgtA)


119899 = 100 119899 = 90

NR3C1 rs41423247(c1184+646CgtG)









Table4Com

paris

onof

geno

type

andallelefre

quencies

offunctio

nalkidneygene

varia

ntsa

ndselected


lower

than

005

arem

arkedwithlowast

Gene

SNP

Genotype

Relap

ses

Frequent

relap

ser()

Age

ofon

set()

Respon

seto

steroids

Treatm

ent

lt5

gt5119901

No

Yes119901

lt3gt3

119901Normal

Slow

NR119901

OnlyGC

IS119901

119899=52119899=25

119899=41119899=40

119899=16119899=65

119899=67119899=13

119899=42119899=39

Angptl4

rs1044

250(c797Cgt

T)

CC20

(38)

11(44)

09426

14(34)

18(44)

04133

8(50)

24(37)

03311

25(37)

6(46)

08494

12(29)

20(51)

00679

CT25

(48)

11(44)

19(46)

18(44)

6(38)

31(48)

32(48)

5(38)

21(50)

16(41)

TT7(13)

3(12)

8(20)

4(10)

2(13)

10(15)

10(15)

2(15)

9(21)

3(8)

C65

(625)

33(66)

07230

47(57)

54(68)

01977

22(69)

79(61)

05416

82(61)

17(65)

08094

45(54)

56(72)

002

28lowast

T39

(375

)17

(34)

35(43)

26(33)

10(31)

51(39)

52(39)

9(35)

39(46)

22(28)

GPC

5rs16946160

(c32

5+1026376GgtA)

GG

47(90)

20(80)

02789

37(90)

33(83)

03493

11(69)

59(91)

00359lowast

58(87)

11(85)

1000

38(90)

32(82)

03389

GA

5(10)

5(20)

4(10)

7(18)

5(31)

6(9)

9(13)

2(15)

4(10)

7(18)

AA

0(0)

0(0)

0(0)

0(0)

0(0)

0(0)

0(0)

0(0)

0(0)

0(0)

G99

(95)

45(90)

02951

78(95)

73(91)

03663

27(84)

124(95)

00421lowast

125(93)

24(92)

06322

80(95)

71(91)

03567

A5(5)

5(10)

4(5)

7(9)

5(16)

6(5)

9(7)

2(8)

4(5)

7(9)

IL13


CC18

(35)

8(32)

08456

10(24)

16(40)

03114

7(44)

19(29)

064

2024

(36)

2(15)

03703

15(36)

11(28)

07568

CA25

(48)

14(56)

24(59)

19(48)

7(44)

35(54)

33(49)

9(69)

21(50)

21(54)

AA

9(17)

3(12)

7(17)

5(13)

2(13)

11(17)

10(15)

2(15)

6(14

)7(18)

C61

(59)

30(60)

1000

44(54)

51(64)

02056

21(66)

73(56)

04246

81(60)

13(50)

1000

51(61)

43(55)

05253

A43

(41)

20(40)

38(46)

29(36)

11(34)

57(44)

53(40)

13(50)

33(39)

35(45)

MIF

rs755622

(c-2

70GgtC)

GG

31(60)

16(64)

1000

26(63)

24(60)

09284

9(56)

40(62)

00634

40(60)

8(62)

1000

25(60)

24(62)

07481

GC

18(35)

8(32)

13(32)

14(35)

7(44)

21(32)

23(34)

5(38)

14(33)

14(36)

CC3(6)

1(4)

2(5)

2(5)

0(0)

4(6)

4(6)

0(0)

3(7)

1(3)

G80

(77)

40(80)

08359

65(79)

62(78)

08497

25(78)

101(78)

1000

103(77)

21(81)

1000

64(76)

62(79)

07063

C24

(23)

10(20)

17(21)

18(23)

7(22)

29(22)

31(23)

5(19)

20(24)

16(21)

nNOS

rs2662826

(clowast276CgtT)

CC24

(46)

10(4)

07393

19(46)

17(43)

02027

5(31)

31(48)

040

8029

(43)

7(54)

06178

19(45)

17(44)

05406

CT23

(44)

11(44)

20(49)

16(40

8(50)

28(43)

31(46)

4(31)

20(48)

16(41)

TT5(10)

4(16)

2(5)

7(18)

3(19

)6(9)

7(10)

2(15)

3(7)

6(15)

C71

(68)

31(62)

04702

58(71)

50(63)

040

7518

(56)

90(69)

02089

89(66)

18(69)

0458

58(69)

50(64)

05103

T33

(32)

19(38)

24(29)

30(38)

14(44)

40(31)

45(34)

8(31)

26(31)

28(36)


Table5Com

paris

onof

geno

type

andallelefre

quencies

ofglucocortic

oidmetabolism

gene

varia

ntsandselected

clinicalfeaturesGC


NR

norespon

seIS

immun

osup

pressiv

edrugs119901

values

lower

than

005

arem

arkedwithlowast

Gene

SNP

Genotype

Relap

ses

Frequent

relap

ser()

Age

ofon

set()

Respon

seto

GC

Treatm

ent

lt5gt5

119901No

Yes

119901lt3gt3

119901Normal

Slow

NR119901

OnlyGCs

IS119901

119899=52119899=25

119899=41119899=40

119899=16119899=65

119899=67119899=13

119899=42119899=39

MDR1

rs1128503

(c12

36Cgt

T)

CC12

(23)

4(16)

02330

9(22)

8(20)

04526

1(6)

16(25)

02863

14(21)

3(23)

1000

12(29)

5(17)

001lowast

CT29

(56)

11(44)

23(56)

18(45)

10(63)

31(48)

34(51)

6(46)

24(57)

7(24)

TT11(21)

10(40)

9(22)

14(35)

5(31)

18(28)

19(28)

4(31)

6(14

)17

(59)

C53

(51)

19(38)

01678

41(50)

34(43)

03496

12(38)

63(48)

03240

62(46)

12(46)

00566

48(57)

17(29)

000

12lowast

T51

(49)

31(62)

41(50)

46(58)

20(63)

67(52)

72(54)

14(54)

36(43)

41(71)

rs2032582

(c2677GgtTA)

GG

9(17)

4(16)

05655

6(15)

7(185)

03793

1(6)

12(18)

03311

12(18)

1(8)

04136

10(24)

3(8)

000

67lowast

GT

25(48)

11(44)

22(54)

17(435)

7(44)

32(49)

32(48)

6(46)

22(53)

17(44)

TT13

(25)

10(40)

9(22)

15(385)

7(44)

17(26)

20(30)

4(31)

6(14

)18

(46)

TA2(4)

0(0)

2(5)

0(0)

1(6)

1(2)

1(1)

1(8)

2(5)

0(0)

GA

3(6)

0(0)

2(5)

1(35)

03(5)

2(3)

1(8)

2(5)

1(3)

G46

(44)

19(38)

01985

36(44)

32(40)

03448

9(28)

59(45)

01642

58(43)

9(35)

00529

44(52)

24(31)

000

28lowast

T53

(51)

31(62)

42(51)

47(59)

22(69)

67(52)

73(54)

15(58)

36(43)

53(68)

A5(6)

0(0)

4(5)

1(1)

1(3)

4(3)

3(3)

2(8)

4(5)

1(1)

rs104564

2(c3435CgtT)

CC9(17)

4(16)

1000

8(20)

5(12)

04179

0(0)

13(20)

003

15lowast

12(18)

1(8)

08447

10(24)

3(8)

003

89lowast

CT23

(44)

11(44)

19(46)

16(39)

11(69)

24(37)

28(42)

6(46)

20(48)

15(38)

TT20

(38)

10(40)

14(34)

19(46)

5(31)

28(43)

27(40)

6(46)

12(29)

21(54)

C41

(39)

19(38)

1000

35(43)

26(33)

11977

11(34)

50(38)

08389

52(39)

8(31)

001

13lowast

40(48)

21(27)

000

92lowast

T63

(61)

31(62)

47(57)

54(68)

21(66)

80(62)

82(61)

18(69)

44(52)

57(73)

GLCC

I1

rs37972(c-1473TgtC)

CC16

(31)

11(44)

04931

13(32)

15(38)

08291

8(50)

20(31)

02289

24(36)

4(31)

1000

11(26)

17(44)

02726

CT26

(50)

11(44)

21(51)

20(50)

5(31)

35(54)

33(49)

7(54)

23(55)

17(44)

TT10

(19)

3(12)

7(17)

5(13)

3(19

)10

(15)

10(15)

2(15)

8(19

)5(13)

C58

(56)

33(66)

02938

47(57)

50(63)

0525

21(66)

75(58)

05473

81(60)

15(58)

1000

45(54)

51(65)

01506

T46

(44)

17(34)

35(43)

30(38)

11(34)

55(42)

53(40)

11(42)

39(46)

27(35)

rs37973(c-1106GgtA)

AA

14(27)

12(48)

0119

712

(29)

15(38)

06024

8(50)

19(29)

01861

22(33)

5(38)

08423

9(21)

18846)

00623

GA

26(50)

11(44)

21(51)

20(50)

5(31)

35(54)

33(49)

7(54)

24(57)

16(41)

GG

12(23)

2(8)

8(20)

5(13

3(19

)11(17)

12(18)

1(8)

9(21)

5(13)

A54

(52)

35(70)

003

77lowast

45(55)

50(63)

03427

21(66)

73(56)

04246

77(57)

17(65)

06321

42(50)

52(67)

00387

G50

(48)

15(30)

37(45)

30(38)

11(34)

57(44)

57(43)

9(35)

42(50)

26(33)

NR3

C1rs41423247

(c1184+6

46Cgt

G)

GG

20(38)

5(20)

001

73lowast

14(34)

11(28)

004

42lowast

5(31)

21(32)

05928

23(34)

2(15)

02363

16(38)

10(26)

00655

GC

17(33)

17(68)

14(34)

24(60)

6(38)

31(48)

31(46)

6(46)

14(33)

23(59)

CC15

(29)

3(12)

13(32)

5(13)

5(31)

13(20)

13(19

)5(38)

12(29)

6(15)

G57

(55)

27(54)

1000

42(51)

46(58)

04352

16(50)

73(56)

05571

77(57)

10(38)

03479

46(55)

43(55)

1000

C47

(45)

23(46)

40(49)

34(43)

16(50)

57(44)

57(43)

16(62)

38(45)

35(45)














GPC5





MDR1











217186 [12] 21218 [22]1123 [30]

GLCCI1


lowastOnly control

5 Conclusion




Competing Interests


References









































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of



















2


119901


GPC5 rs16946160(c325+1026376GgtA)

GG 88 884 041 gt005 86 856 025 gt005GA 12 113 14 147AA 0 04 1 06




MDR1


rs2032582(c2677GgtTA)



GLCCI1



NR3C1 rs41423247(c1184+646CgtG)

GG 32 308 024 gt005 37 342 153 gt005GC 47 494 37 426CC 21 198 16 132







119899 = 100 119899 = 84



119899 = 100 119899 = 101

GPC5 rs16946160(c325+1026376GgtA)



119899 = 100 119899 = 101




119899 = 100 119899 = 101



119899 = 100 119899 = 99



119899 = 100 119899 = 98

MDR1

rs1128503(c1236CgtT)


119899 = 100 119899 = 98

rs2032582(c2677GgtTA)


119899 = 100 119899 = 98

rs1045642(c3435CgtT)



Table 3 Continued


119899 = 100 119899 = 97

GLCCI1

rs37972 (c-1473TgtC)


119899 = 100 119899 = 90

rs37973 (c-1106GgtA)


119899 = 100 119899 = 90

NR3C1 rs41423247(c1184+646CgtG)









Table4Com

paris

onof

geno

type

andallelefre

quencies

offunctio

nalkidneygene

varia

ntsa

ndselected


lower

than

005

arem

arkedwithlowast

Gene

SNP

Genotype

Relap

ses

Frequent

relap

ser()

Age

ofon

set()

Respon

seto

steroids

Treatm

ent

lt5

gt5119901

No

Yes119901

lt3gt3

119901Normal

Slow

NR119901

OnlyGC

IS119901

119899=52119899=25

119899=41119899=40

119899=16119899=65

119899=67119899=13

119899=42119899=39

Angptl4

rs1044

250(c797Cgt

T)

CC20

(38)

11(44)

09426

14(34)

18(44)

04133

8(50)

24(37)

03311

25(37)

6(46)

08494

12(29)

20(51)

00679

CT25

(48)

11(44)

19(46)

18(44)

6(38)

31(48)

32(48)

5(38)

21(50)

16(41)

TT7(13)

3(12)

8(20)

4(10)

2(13)

10(15)

10(15)

2(15)

9(21)

3(8)

C65

(625)

33(66)

07230

47(57)

54(68)

01977

22(69)

79(61)

05416

82(61)

17(65)

08094

45(54)

56(72)

002

28lowast

T39

(375

)17

(34)

35(43)

26(33)

10(31)

51(39)

52(39)

9(35)

39(46)

22(28)

GPC

5rs16946160

(c32

5+1026376GgtA)

GG

47(90)

20(80)

02789

37(90)

33(83)

03493

11(69)

59(91)

00359lowast

58(87)

11(85)

1000

38(90)

32(82)

03389

GA

5(10)

5(20)

4(10)

7(18)

5(31)

6(9)

9(13)

2(15)

4(10)

7(18)

AA

0(0)

0(0)

0(0)

0(0)

0(0)

0(0)

0(0)

0(0)

0(0)

0(0)

G99

(95)

45(90)

02951

78(95)

73(91)

03663

27(84)

124(95)

00421lowast

125(93)

24(92)

06322

80(95)

71(91)

03567

A5(5)

5(10)

4(5)

7(9)

5(16)

6(5)

9(7)

2(8)

4(5)

7(9)

IL13


CC18

(35)

8(32)

08456

10(24)

16(40)

03114

7(44)

19(29)

064

2024

(36)

2(15)

03703

15(36)

11(28)

07568

CA25

(48)

14(56)

24(59)

19(48)

7(44)

35(54)

33(49)

9(69)

21(50)

21(54)

AA

9(17)

3(12)

7(17)

5(13)

2(13)

11(17)

10(15)

2(15)

6(14

)7(18)

C61

(59)

30(60)

1000

44(54)

51(64)

02056

21(66)

73(56)

04246

81(60)

13(50)

1000

51(61)

43(55)

05253

A43

(41)

20(40)

38(46)

29(36)

11(34)

57(44)

53(40)

13(50)

33(39)

35(45)

MIF

rs755622

(c-2

70GgtC)

GG

31(60)

16(64)

1000

26(63)

24(60)

09284

9(56)

40(62)

00634

40(60)

8(62)

1000

25(60)

24(62)

07481

GC

18(35)

8(32)

13(32)

14(35)

7(44)

21(32)

23(34)

5(38)

14(33)

14(36)

CC3(6)

1(4)

2(5)

2(5)

0(0)

4(6)

4(6)

0(0)

3(7)

1(3)

G80

(77)

40(80)

08359

65(79)

62(78)

08497

25(78)

101(78)

1000

103(77)

21(81)

1000

64(76)

62(79)

07063

C24

(23)

10(20)

17(21)

18(23)

7(22)

29(22)

31(23)

5(19)

20(24)

16(21)

nNOS

rs2662826

(clowast276CgtT)

CC24

(46)

10(4)

07393

19(46)

17(43)

02027

5(31)

31(48)

040

8029

(43)

7(54)

06178

19(45)

17(44)

05406

CT23

(44)

11(44)

20(49)

16(40

8(50)

28(43)

31(46)

4(31)

20(48)

16(41)

TT5(10)

4(16)

2(5)

7(18)

3(19

)6(9)

7(10)

2(15)

3(7)

6(15)

C71

(68)

31(62)

04702

58(71)

50(63)

040

7518

(56)

90(69)

02089

89(66)

18(69)

0458

58(69)

50(64)

05103

T33

(32)

19(38)

24(29)

30(38)

14(44)

40(31)

45(34)

8(31)

26(31)

28(36)


Table5Com

paris

onof

geno

type

andallelefre

quencies

ofglucocortic

oidmetabolism

gene

varia

ntsandselected

clinicalfeaturesGC


NR

norespon

seIS

immun

osup

pressiv

edrugs119901

values

lower

than

005

arem

arkedwithlowast

Gene

SNP

Genotype

Relap

ses

Frequent

relap

ser()

Age

ofon

set()

Respon

seto

GC

Treatm

ent

lt5gt5

119901No

Yes

119901lt3gt3

119901Normal

Slow

NR119901

OnlyGCs

IS119901

119899=52119899=25

119899=41119899=40

119899=16119899=65

119899=67119899=13

119899=42119899=39

MDR1

rs1128503

(c12

36Cgt

T)

CC12

(23)

4(16)

02330

9(22)

8(20)

04526

1(6)

16(25)

02863

14(21)

3(23)

1000

12(29)

5(17)

001lowast

CT29

(56)

11(44)

23(56)

18(45)

10(63)

31(48)

34(51)

6(46)

24(57)

7(24)

TT11(21)

10(40)

9(22)

14(35)

5(31)

18(28)

19(28)

4(31)

6(14

)17

(59)

C53

(51)

19(38)

01678

41(50)

34(43)

03496

12(38)

63(48)

03240

62(46)

12(46)

00566

48(57)

17(29)

000

12lowast

T51

(49)

31(62)

41(50)

46(58)

20(63)

67(52)

72(54)

14(54)

36(43)

41(71)

rs2032582

(c2677GgtTA)

GG

9(17)

4(16)

05655

6(15)

7(185)

03793

1(6)

12(18)

03311

12(18)

1(8)

04136

10(24)

3(8)

000

67lowast

GT

25(48)

11(44)

22(54)

17(435)

7(44)

32(49)

32(48)

6(46)

22(53)

17(44)

TT13

(25)

10(40)

9(22)

15(385)

7(44)

17(26)

20(30)

4(31)

6(14

)18

(46)

TA2(4)

0(0)

2(5)

0(0)

1(6)

1(2)

1(1)

1(8)

2(5)

0(0)

GA

3(6)

0(0)

2(5)

1(35)

03(5)

2(3)

1(8)

2(5)

1(3)

G46

(44)

19(38)

01985

36(44)

32(40)

03448

9(28)

59(45)

01642

58(43)

9(35)

00529

44(52)

24(31)

000

28lowast

T53

(51)

31(62)

42(51)

47(59)

22(69)

67(52)

73(54)

15(58)

36(43)

53(68)

A5(6)

0(0)

4(5)

1(1)

1(3)

4(3)

3(3)

2(8)

4(5)

1(1)

rs104564

2(c3435CgtT)

CC9(17)

4(16)

1000

8(20)

5(12)

04179

0(0)

13(20)

003

15lowast

12(18)

1(8)

08447

10(24)

3(8)

003

89lowast

CT23

(44)

11(44)

19(46)

16(39)

11(69)

24(37)

28(42)

6(46)

20(48)

15(38)

TT20

(38)

10(40)

14(34)

19(46)

5(31)

28(43)

27(40)

6(46)

12(29)

21(54)

C41

(39)

19(38)

1000

35(43)

26(33)

11977

11(34)

50(38)

08389

52(39)

8(31)

001

13lowast

40(48)

21(27)

000

92lowast

T63

(61)

31(62)

47(57)

54(68)

21(66)

80(62)

82(61)

18(69)

44(52)

57(73)

GLCC

I1

rs37972(c-1473TgtC)

CC16

(31)

11(44)

04931

13(32)

15(38)

08291

8(50)

20(31)

02289

24(36)

4(31)

1000

11(26)

17(44)

02726

CT26

(50)

11(44)

21(51)

20(50)

5(31)

35(54)

33(49)

7(54)

23(55)

17(44)

TT10

(19)

3(12)

7(17)

5(13)

3(19

)10

(15)

10(15)

2(15)

8(19

)5(13)

C58

(56)

33(66)

02938

47(57)

50(63)

0525

21(66)

75(58)

05473

81(60)

15(58)

1000

45(54)

51(65)

01506

T46

(44)

17(34)

35(43)

30(38)

11(34)

55(42)

53(40)

11(42)

39(46)

27(35)

rs37973(c-1106GgtA)

AA

14(27)

12(48)

0119

712

(29)

15(38)

06024

8(50)

19(29)

01861

22(33)

5(38)

08423

9(21)

18846)

00623

GA

26(50)

11(44)

21(51)

20(50)

5(31)

35(54)

33(49)

7(54)

24(57)

16(41)

GG

12(23)

2(8)

8(20)

5(13

3(19

)11(17)

12(18)

1(8)

9(21)

5(13)

A54

(52)

35(70)

003

77lowast

45(55)

50(63)

03427

21(66)

73(56)

04246

77(57)

17(65)

06321

42(50)

52(67)

00387

G50

(48)

15(30)

37(45)

30(38)

11(34)

57(44)

57(43)

9(35)

42(50)

26(33)

NR3

C1rs41423247

(c1184+6

46Cgt

G)

GG

20(38)

5(20)

001

73lowast

14(34)

11(28)

004

42lowast

5(31)

21(32)

05928

23(34)

2(15)

02363

16(38)

10(26)

00655

GC

17(33)

17(68)

14(34)

24(60)

6(38)

31(48)

31(46)

6(46)

14(33)

23(59)

CC15

(29)

3(12)

13(32)

5(13)

5(31)

13(20)

13(19

)5(38)

12(29)

6(15)

G57

(55)

27(54)

1000

42(51)

46(58)

04352

16(50)

73(56)

05571

77(57)

10(38)

03479

46(55)

43(55)

1000

C47

(45)

23(46)

40(49)

34(43)

16(50)

57(44)

57(43)

16(62)

38(45)

35(45)














GPC5





MDR1











217186 [12] 21218 [22]1123 [30]

GLCCI1


lowastOnly control

5 Conclusion




Competing Interests


References









































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of



















119899 = 100 119899 = 84



119899 = 100 119899 = 101

GPC5 rs16946160(c325+1026376GgtA)



119899 = 100 119899 = 101




119899 = 100 119899 = 101



119899 = 100 119899 = 99



119899 = 100 119899 = 98

MDR1

rs1128503(c1236CgtT)


119899 = 100 119899 = 98

rs2032582(c2677GgtTA)


119899 = 100 119899 = 98

rs1045642(c3435CgtT)



Table 3 Continued


119899 = 100 119899 = 97

GLCCI1

rs37972 (c-1473TgtC)


119899 = 100 119899 = 90

rs37973 (c-1106GgtA)


119899 = 100 119899 = 90

NR3C1 rs41423247(c1184+646CgtG)









Table4Com

paris

onof

geno

type

andallelefre

quencies

offunctio

nalkidneygene

varia

ntsa

ndselected


lower

than

005

arem

arkedwithlowast

Gene

SNP

Genotype

Relap

ses

Frequent

relap

ser()

Age

ofon

set()

Respon

seto

steroids

Treatm

ent

lt5

gt5119901

No

Yes119901

lt3gt3

119901Normal

Slow

NR119901

OnlyGC

IS119901

119899=52119899=25

119899=41119899=40

119899=16119899=65

119899=67119899=13

119899=42119899=39

Angptl4

rs1044

250(c797Cgt

T)

CC20

(38)

11(44)

09426

14(34)

18(44)

04133

8(50)

24(37)

03311

25(37)

6(46)

08494

12(29)

20(51)

00679

CT25

(48)

11(44)

19(46)

18(44)

6(38)

31(48)

32(48)

5(38)

21(50)

16(41)

TT7(13)

3(12)

8(20)

4(10)

2(13)

10(15)

10(15)

2(15)

9(21)

3(8)

C65

(625)

33(66)

07230

47(57)

54(68)

01977

22(69)

79(61)

05416

82(61)

17(65)

08094

45(54)

56(72)

002

28lowast

T39

(375

)17

(34)

35(43)

26(33)

10(31)

51(39)

52(39)

9(35)

39(46)

22(28)

GPC

5rs16946160

(c32

5+1026376GgtA)

GG

47(90)

20(80)

02789

37(90)

33(83)

03493

11(69)

59(91)

00359lowast

58(87)

11(85)

1000

38(90)

32(82)

03389

GA

5(10)

5(20)

4(10)

7(18)

5(31)

6(9)

9(13)

2(15)

4(10)

7(18)

AA

0(0)

0(0)

0(0)

0(0)

0(0)

0(0)

0(0)

0(0)

0(0)

0(0)

G99

(95)

45(90)

02951

78(95)

73(91)

03663

27(84)

124(95)

00421lowast

125(93)

24(92)

06322

80(95)

71(91)

03567

A5(5)

5(10)

4(5)

7(9)

5(16)

6(5)

9(7)

2(8)

4(5)

7(9)

IL13


CC18

(35)

8(32)

08456

10(24)

16(40)

03114

7(44)

19(29)

064

2024

(36)

2(15)

03703

15(36)

11(28)

07568

CA25

(48)

14(56)

24(59)

19(48)

7(44)

35(54)

33(49)

9(69)

21(50)

21(54)

AA

9(17)

3(12)

7(17)

5(13)

2(13)

11(17)

10(15)

2(15)

6(14

)7(18)

C61

(59)

30(60)

1000

44(54)

51(64)

02056

21(66)

73(56)

04246

81(60)

13(50)

1000

51(61)

43(55)

05253

A43

(41)

20(40)

38(46)

29(36)

11(34)

57(44)

53(40)

13(50)

33(39)

35(45)

MIF

rs755622

(c-2

70GgtC)

GG

31(60)

16(64)

1000

26(63)

24(60)

09284

9(56)

40(62)

00634

40(60)

8(62)

1000

25(60)

24(62)

07481

GC

18(35)

8(32)

13(32)

14(35)

7(44)

21(32)

23(34)

5(38)

14(33)

14(36)

CC3(6)

1(4)

2(5)

2(5)

0(0)

4(6)

4(6)

0(0)

3(7)

1(3)

G80

(77)

40(80)

08359

65(79)

62(78)

08497

25(78)

101(78)

1000

103(77)

21(81)

1000

64(76)

62(79)

07063

C24

(23)

10(20)

17(21)

18(23)

7(22)

29(22)

31(23)

5(19)

20(24)

16(21)

nNOS

rs2662826

(clowast276CgtT)

CC24

(46)

10(4)

07393

19(46)

17(43)

02027

5(31)

31(48)

040

8029

(43)

7(54)

06178

19(45)

17(44)

05406

CT23

(44)

11(44)

20(49)

16(40

8(50)

28(43)

31(46)

4(31)

20(48)

16(41)

TT5(10)

4(16)

2(5)

7(18)

3(19

)6(9)

7(10)

2(15)

3(7)

6(15)

C71

(68)

31(62)

04702

58(71)

50(63)

040

7518

(56)

90(69)

02089

89(66)

18(69)

0458

58(69)

50(64)

05103

T33

(32)

19(38)

24(29)

30(38)

14(44)

40(31)

45(34)

8(31)

26(31)

28(36)


Table5Com

paris

onof

geno

type

andallelefre

quencies

ofglucocortic

oidmetabolism

gene

varia

ntsandselected

clinicalfeaturesGC


NR

norespon

seIS

immun

osup

pressiv

edrugs119901

values

lower

than

005

arem

arkedwithlowast

Gene

SNP

Genotype

Relap

ses

Frequent

relap

ser()

Age

ofon

set()

Respon

seto

GC

Treatm

ent

lt5gt5

119901No

Yes

119901lt3gt3

119901Normal

Slow

NR119901

OnlyGCs

IS119901

119899=52119899=25

119899=41119899=40

119899=16119899=65

119899=67119899=13

119899=42119899=39

MDR1

rs1128503

(c12

36Cgt

T)

CC12

(23)

4(16)

02330

9(22)

8(20)

04526

1(6)

16(25)

02863

14(21)

3(23)

1000

12(29)

5(17)

001lowast

CT29

(56)

11(44)

23(56)

18(45)

10(63)

31(48)

34(51)

6(46)

24(57)

7(24)

TT11(21)

10(40)

9(22)

14(35)

5(31)

18(28)

19(28)

4(31)

6(14

)17

(59)

C53

(51)

19(38)

01678

41(50)

34(43)

03496

12(38)

63(48)

03240

62(46)

12(46)

00566

48(57)

17(29)

000

12lowast

T51

(49)

31(62)

41(50)

46(58)

20(63)

67(52)

72(54)

14(54)

36(43)

41(71)

rs2032582

(c2677GgtTA)

GG

9(17)

4(16)

05655

6(15)

7(185)

03793

1(6)

12(18)

03311

12(18)

1(8)

04136

10(24)

3(8)

000

67lowast

GT

25(48)

11(44)

22(54)

17(435)

7(44)

32(49)

32(48)

6(46)

22(53)

17(44)

TT13

(25)

10(40)

9(22)

15(385)

7(44)

17(26)

20(30)

4(31)

6(14

)18

(46)

TA2(4)

0(0)

2(5)

0(0)

1(6)

1(2)

1(1)

1(8)

2(5)

0(0)

GA

3(6)

0(0)

2(5)

1(35)

03(5)

2(3)

1(8)

2(5)

1(3)

G46

(44)

19(38)

01985

36(44)

32(40)

03448

9(28)

59(45)

01642

58(43)

9(35)

00529

44(52)

24(31)

000

28lowast

T53

(51)

31(62)

42(51)

47(59)

22(69)

67(52)

73(54)

15(58)

36(43)

53(68)

A5(6)

0(0)

4(5)

1(1)

1(3)

4(3)

3(3)

2(8)

4(5)

1(1)

rs104564

2(c3435CgtT)

CC9(17)

4(16)

1000

8(20)

5(12)

04179

0(0)

13(20)

003

15lowast

12(18)

1(8)

08447

10(24)

3(8)

003

89lowast

CT23

(44)

11(44)

19(46)

16(39)

11(69)

24(37)

28(42)

6(46)

20(48)

15(38)

TT20

(38)

10(40)

14(34)

19(46)

5(31)

28(43)

27(40)

6(46)

12(29)

21(54)

C41

(39)

19(38)

1000

35(43)

26(33)

11977

11(34)

50(38)

08389

52(39)

8(31)

001

13lowast

40(48)

21(27)

000

92lowast

T63

(61)

31(62)

47(57)

54(68)

21(66)

80(62)

82(61)

18(69)

44(52)

57(73)

GLCC

I1

rs37972(c-1473TgtC)

CC16

(31)

11(44)

04931

13(32)

15(38)

08291

8(50)

20(31)

02289

24(36)

4(31)

1000

11(26)

17(44)

02726

CT26

(50)

11(44)

21(51)

20(50)

5(31)

35(54)

33(49)

7(54)

23(55)

17(44)

TT10

(19)

3(12)

7(17)

5(13)

3(19

)10

(15)

10(15)

2(15)

8(19

)5(13)

C58

(56)

33(66)

02938

47(57)

50(63)

0525

21(66)

75(58)

05473

81(60)

15(58)

1000

45(54)

51(65)

01506

T46

(44)

17(34)

35(43)

30(38)

11(34)

55(42)

53(40)

11(42)

39(46)

27(35)

rs37973(c-1106GgtA)

AA

14(27)

12(48)

0119

712

(29)

15(38)

06024

8(50)

19(29)

01861

22(33)

5(38)

08423

9(21)

18846)

00623

GA

26(50)

11(44)

21(51)

20(50)

5(31)

35(54)

33(49)

7(54)

24(57)

16(41)

GG

12(23)

2(8)

8(20)

5(13

3(19

)11(17)

12(18)

1(8)

9(21)

5(13)

A54

(52)

35(70)

003

77lowast

45(55)

50(63)

03427

21(66)

73(56)

04246

77(57)

17(65)

06321

42(50)

52(67)

00387

G50

(48)

15(30)

37(45)

30(38)

11(34)

57(44)

57(43)

9(35)

42(50)

26(33)

NR3

C1rs41423247

(c1184+6

46Cgt

G)

GG

20(38)

5(20)

001

73lowast

14(34)

11(28)

004

42lowast

5(31)

21(32)

05928

23(34)

2(15)

02363

16(38)

10(26)

00655

GC

17(33)

17(68)

14(34)

24(60)

6(38)

31(48)

31(46)

6(46)

14(33)

23(59)

CC15

(29)

3(12)

13(32)

5(13)

5(31)

13(20)

13(19

)5(38)

12(29)

6(15)

G57

(55)

27(54)

1000

42(51)

46(58)

04352

16(50)

73(56)

05571

77(57)

10(38)

03479

46(55)

43(55)

1000

C47

(45)

23(46)

40(49)

34(43)

16(50)

57(44)

57(43)

16(62)

38(45)

35(45)














GPC5





MDR1











217186 [12] 21218 [22]1123 [30]

GLCCI1


lowastOnly control

5 Conclusion




Competing Interests


References









































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of

















Table 3 Continued


119899 = 100 119899 = 97

GLCCI1

rs37972 (c-1473TgtC)


119899 = 100 119899 = 90

rs37973 (c-1106GgtA)


119899 = 100 119899 = 90

NR3C1 rs41423247(c1184+646CgtG)









Table4Com

paris

onof

geno

type

andallelefre

quencies

offunctio

nalkidneygene

varia

ntsa

ndselected


lower

than

005

arem

arkedwithlowast

Gene

SNP

Genotype

Relap

ses

Frequent

relap

ser()

Age

ofon

set()

Respon

seto

steroids

Treatm

ent

lt5

gt5119901

No

Yes119901

lt3gt3

119901Normal

Slow

NR119901

OnlyGC

IS119901

119899=52119899=25

119899=41119899=40

119899=16119899=65

119899=67119899=13

119899=42119899=39

Angptl4

rs1044

250(c797Cgt

T)

CC20

(38)

11(44)

09426

14(34)

18(44)

04133

8(50)

24(37)

03311

25(37)

6(46)

08494

12(29)

20(51)

00679

CT25

(48)

11(44)

19(46)

18(44)

6(38)

31(48)

32(48)

5(38)

21(50)

16(41)

TT7(13)

3(12)

8(20)

4(10)

2(13)

10(15)

10(15)

2(15)

9(21)

3(8)

C65

(625)

33(66)

07230

47(57)

54(68)

01977

22(69)

79(61)

05416

82(61)

17(65)

08094

45(54)

56(72)

002

28lowast

T39

(375

)17

(34)

35(43)

26(33)

10(31)

51(39)

52(39)

9(35)

39(46)

22(28)

GPC

5rs16946160

(c32

5+1026376GgtA)

GG

47(90)

20(80)

02789

37(90)

33(83)

03493

11(69)

59(91)

00359lowast

58(87)

11(85)

1000

38(90)

32(82)

03389

GA

5(10)

5(20)

4(10)

7(18)

5(31)

6(9)

9(13)

2(15)

4(10)

7(18)

AA

0(0)

0(0)

0(0)

0(0)

0(0)

0(0)

0(0)

0(0)

0(0)

0(0)

G99

(95)

45(90)

02951

78(95)

73(91)

03663

27(84)

124(95)

00421lowast

125(93)

24(92)

06322

80(95)

71(91)

03567

A5(5)

5(10)

4(5)

7(9)

5(16)

6(5)

9(7)

2(8)

4(5)

7(9)

IL13


CC18

(35)

8(32)

08456

10(24)

16(40)

03114

7(44)

19(29)

064

2024

(36)

2(15)

03703

15(36)

11(28)

07568

CA25

(48)

14(56)

24(59)

19(48)

7(44)

35(54)

33(49)

9(69)

21(50)

21(54)

AA

9(17)

3(12)

7(17)

5(13)

2(13)

11(17)

10(15)

2(15)

6(14

)7(18)

C61

(59)

30(60)

1000

44(54)

51(64)

02056

21(66)

73(56)

04246

81(60)

13(50)

1000

51(61)

43(55)

05253

A43

(41)

20(40)

38(46)

29(36)

11(34)

57(44)

53(40)

13(50)

33(39)

35(45)

MIF

rs755622

(c-2

70GgtC)

GG

31(60)

16(64)

1000

26(63)

24(60)

09284

9(56)

40(62)

00634

40(60)

8(62)

1000

25(60)

24(62)

07481

GC

18(35)

8(32)

13(32)

14(35)

7(44)

21(32)

23(34)

5(38)

14(33)

14(36)

CC3(6)

1(4)

2(5)

2(5)

0(0)

4(6)

4(6)

0(0)

3(7)

1(3)

G80

(77)

40(80)

08359

65(79)

62(78)

08497

25(78)

101(78)

1000

103(77)

21(81)

1000

64(76)

62(79)

07063

C24

(23)

10(20)

17(21)

18(23)

7(22)

29(22)

31(23)

5(19)

20(24)

16(21)

nNOS

rs2662826

(clowast276CgtT)

CC24

(46)

10(4)

07393

19(46)

17(43)

02027

5(31)

31(48)

040

8029

(43)

7(54)

06178

19(45)

17(44)

05406

CT23

(44)

11(44)

20(49)

16(40

8(50)

28(43)

31(46)

4(31)

20(48)

16(41)

TT5(10)

4(16)

2(5)

7(18)

3(19

)6(9)

7(10)

2(15)

3(7)

6(15)

C71

(68)

31(62)

04702

58(71)

50(63)

040

7518

(56)

90(69)

02089

89(66)

18(69)

0458

58(69)

50(64)

05103

T33

(32)

19(38)

24(29)

30(38)

14(44)

40(31)

45(34)

8(31)

26(31)

28(36)


Table5Com

paris

onof

geno

type

andallelefre

quencies

ofglucocortic

oidmetabolism

gene

varia

ntsandselected

clinicalfeaturesGC


NR

norespon

seIS

immun

osup

pressiv

edrugs119901

values

lower

than

005

arem

arkedwithlowast

Gene

SNP

Genotype

Relap

ses

Frequent

relap

ser()

Age

ofon

set()

Respon

seto

GC

Treatm

ent

lt5gt5

119901No

Yes

119901lt3gt3

119901Normal

Slow

NR119901

OnlyGCs

IS119901

119899=52119899=25

119899=41119899=40

119899=16119899=65

119899=67119899=13

119899=42119899=39

MDR1

rs1128503

(c12

36Cgt

T)

CC12

(23)

4(16)

02330

9(22)

8(20)

04526

1(6)

16(25)

02863

14(21)

3(23)

1000

12(29)

5(17)

001lowast

CT29

(56)

11(44)

23(56)

18(45)

10(63)

31(48)

34(51)

6(46)

24(57)

7(24)

TT11(21)

10(40)

9(22)

14(35)

5(31)

18(28)

19(28)

4(31)

6(14

)17

(59)

C53

(51)

19(38)

01678

41(50)

34(43)

03496

12(38)

63(48)

03240

62(46)

12(46)

00566

48(57)

17(29)

000

12lowast

T51

(49)

31(62)

41(50)

46(58)

20(63)

67(52)

72(54)

14(54)

36(43)

41(71)

rs2032582

(c2677GgtTA)

GG

9(17)

4(16)

05655

6(15)

7(185)

03793

1(6)

12(18)

03311

12(18)

1(8)

04136

10(24)

3(8)

000

67lowast

GT

25(48)

11(44)

22(54)

17(435)

7(44)

32(49)

32(48)

6(46)

22(53)

17(44)

TT13

(25)

10(40)

9(22)

15(385)

7(44)

17(26)

20(30)

4(31)

6(14

)18

(46)

TA2(4)

0(0)

2(5)

0(0)

1(6)

1(2)

1(1)

1(8)

2(5)

0(0)

GA

3(6)

0(0)

2(5)

1(35)

03(5)

2(3)

1(8)

2(5)

1(3)

G46

(44)

19(38)

01985

36(44)

32(40)

03448

9(28)

59(45)

01642

58(43)

9(35)

00529

44(52)

24(31)

000

28lowast

T53

(51)

31(62)

42(51)

47(59)

22(69)

67(52)

73(54)

15(58)

36(43)

53(68)

A5(6)

0(0)

4(5)

1(1)

1(3)

4(3)

3(3)

2(8)

4(5)

1(1)

rs104564

2(c3435CgtT)

CC9(17)

4(16)

1000

8(20)

5(12)

04179

0(0)

13(20)

003

15lowast

12(18)

1(8)

08447

10(24)

3(8)

003

89lowast

CT23

(44)

11(44)

19(46)

16(39)

11(69)

24(37)

28(42)

6(46)

20(48)

15(38)

TT20

(38)

10(40)

14(34)

19(46)

5(31)

28(43)

27(40)

6(46)

12(29)

21(54)

C41

(39)

19(38)

1000

35(43)

26(33)

11977

11(34)

50(38)

08389

52(39)

8(31)

001

13lowast

40(48)

21(27)

000

92lowast

T63

(61)

31(62)

47(57)

54(68)

21(66)

80(62)

82(61)

18(69)

44(52)

57(73)

GLCC

I1

rs37972(c-1473TgtC)

CC16

(31)

11(44)

04931

13(32)

15(38)

08291

8(50)

20(31)

02289

24(36)

4(31)

1000

11(26)

17(44)

02726

CT26

(50)

11(44)

21(51)

20(50)

5(31)

35(54)

33(49)

7(54)

23(55)

17(44)

TT10

(19)

3(12)

7(17)

5(13)

3(19

)10

(15)

10(15)

2(15)

8(19

)5(13)

C58

(56)

33(66)

02938

47(57)

50(63)

0525

21(66)

75(58)

05473

81(60)

15(58)

1000

45(54)

51(65)

01506

T46

(44)

17(34)

35(43)

30(38)

11(34)

55(42)

53(40)

11(42)

39(46)

27(35)

rs37973(c-1106GgtA)

AA

14(27)

12(48)

0119

712

(29)

15(38)

06024

8(50)

19(29)

01861

22(33)

5(38)

08423

9(21)

18846)

00623

GA

26(50)

11(44)

21(51)

20(50)

5(31)

35(54)

33(49)

7(54)

24(57)

16(41)

GG

12(23)

2(8)

8(20)

5(13

3(19

)11(17)

12(18)

1(8)

9(21)

5(13)

A54

(52)

35(70)

003

77lowast

45(55)

50(63)

03427

21(66)

73(56)

04246

77(57)

17(65)

06321

42(50)

52(67)

00387

G50

(48)

15(30)

37(45)

30(38)

11(34)

57(44)

57(43)

9(35)

42(50)

26(33)

NR3

C1rs41423247

(c1184+6

46Cgt

G)

GG

20(38)

5(20)

001

73lowast

14(34)

11(28)

004

42lowast

5(31)

21(32)

05928

23(34)

2(15)

02363

16(38)

10(26)

00655

GC

17(33)

17(68)

14(34)

24(60)

6(38)

31(48)

31(46)

6(46)

14(33)

23(59)

CC15

(29)

3(12)

13(32)

5(13)

5(31)

13(20)

13(19

)5(38)

12(29)

6(15)

G57

(55)

27(54)

1000

42(51)

46(58)

04352

16(50)

73(56)

05571

77(57)

10(38)

03479

46(55)

43(55)

1000

C47

(45)

23(46)

40(49)

34(43)

16(50)

57(44)

57(43)

16(62)

38(45)

35(45)














GPC5





MDR1











217186 [12] 21218 [22]1123 [30]

GLCCI1


lowastOnly control

5 Conclusion




Competing Interests


References









































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of

















Table4Com

paris

onof

geno

type

andallelefre

quencies

offunctio

nalkidneygene

varia

ntsa

ndselected


lower

than

005

arem

arkedwithlowast

Gene

SNP

Genotype

Relap

ses

Frequent

relap

ser()

Age

ofon

set()

Respon

seto

steroids

Treatm

ent

lt5

gt5119901

No

Yes119901

lt3gt3

119901Normal

Slow

NR119901

OnlyGC

IS119901

119899=52119899=25

119899=41119899=40

119899=16119899=65

119899=67119899=13

119899=42119899=39

Angptl4

rs1044

250(c797Cgt

T)

CC20

(38)

11(44)

09426

14(34)

18(44)

04133

8(50)

24(37)

03311

25(37)

6(46)

08494

12(29)

20(51)

00679

CT25

(48)

11(44)

19(46)

18(44)

6(38)

31(48)

32(48)

5(38)

21(50)

16(41)

TT7(13)

3(12)

8(20)

4(10)

2(13)

10(15)

10(15)

2(15)

9(21)

3(8)

C65

(625)

33(66)

07230

47(57)

54(68)

01977

22(69)

79(61)

05416

82(61)

17(65)

08094

45(54)

56(72)

002

28lowast

T39

(375

)17

(34)

35(43)

26(33)

10(31)

51(39)

52(39)

9(35)

39(46)

22(28)

GPC

5rs16946160

(c32

5+1026376GgtA)

GG

47(90)

20(80)

02789

37(90)

33(83)

03493

11(69)

59(91)

00359lowast

58(87)

11(85)

1000

38(90)

32(82)

03389

GA

5(10)

5(20)

4(10)

7(18)

5(31)

6(9)

9(13)

2(15)

4(10)

7(18)

AA

0(0)

0(0)

0(0)

0(0)

0(0)

0(0)

0(0)

0(0)

0(0)

0(0)

G99

(95)

45(90)

02951

78(95)

73(91)

03663

27(84)

124(95)

00421lowast

125(93)

24(92)

06322

80(95)

71(91)

03567

A5(5)

5(10)

4(5)

7(9)

5(16)

6(5)

9(7)

2(8)

4(5)

7(9)

IL13


CC18

(35)

8(32)

08456

10(24)

16(40)

03114

7(44)

19(29)

064

2024

(36)

2(15)

03703

15(36)

11(28)

07568

CA25

(48)

14(56)

24(59)

19(48)

7(44)

35(54)

33(49)

9(69)

21(50)

21(54)

AA

9(17)

3(12)

7(17)

5(13)

2(13)

11(17)

10(15)

2(15)

6(14

)7(18)

C61

(59)

30(60)

1000

44(54)

51(64)

02056

21(66)

73(56)

04246

81(60)

13(50)

1000

51(61)

43(55)

05253

A43

(41)

20(40)

38(46)

29(36)

11(34)

57(44)

53(40)

13(50)

33(39)

35(45)

MIF

rs755622

(c-2

70GgtC)

GG

31(60)

16(64)

1000

26(63)

24(60)

09284

9(56)

40(62)

00634

40(60)

8(62)

1000

25(60)

24(62)

07481

GC

18(35)

8(32)

13(32)

14(35)

7(44)

21(32)

23(34)

5(38)

14(33)

14(36)

CC3(6)

1(4)

2(5)

2(5)

0(0)

4(6)

4(6)

0(0)

3(7)

1(3)

G80

(77)

40(80)

08359

65(79)

62(78)

08497

25(78)

101(78)

1000

103(77)

21(81)

1000

64(76)

62(79)

07063

C24

(23)

10(20)

17(21)

18(23)

7(22)

29(22)

31(23)

5(19)

20(24)

16(21)

nNOS

rs2662826

(clowast276CgtT)

CC24

(46)

10(4)

07393

19(46)

17(43)

02027

5(31)

31(48)

040

8029

(43)

7(54)

06178

19(45)

17(44)

05406

CT23

(44)

11(44)

20(49)

16(40

8(50)

28(43)

31(46)

4(31)

20(48)

16(41)

TT5(10)

4(16)

2(5)

7(18)

3(19

)6(9)

7(10)

2(15)

3(7)

6(15)

C71

(68)

31(62)

04702

58(71)

50(63)

040

7518

(56)

90(69)

02089

89(66)

18(69)

0458

58(69)

50(64)

05103

T33

(32)

19(38)

24(29)

30(38)

14(44)

40(31)

45(34)

8(31)

26(31)

28(36)


Table5Com

paris

onof

geno

type

andallelefre

quencies

ofglucocortic

oidmetabolism

gene

varia

ntsandselected

clinicalfeaturesGC


NR

norespon

seIS

immun

osup

pressiv

edrugs119901

values

lower

than

005

arem

arkedwithlowast

Gene

SNP

Genotype

Relap

ses

Frequent

relap

ser()

Age

ofon

set()

Respon

seto

GC

Treatm

ent

lt5gt5

119901No

Yes

119901lt3gt3

119901Normal

Slow

NR119901

OnlyGCs

IS119901

119899=52119899=25

119899=41119899=40

119899=16119899=65

119899=67119899=13

119899=42119899=39

MDR1

rs1128503

(c12

36Cgt

T)

CC12

(23)

4(16)

02330

9(22)

8(20)

04526

1(6)

16(25)

02863

14(21)

3(23)

1000

12(29)

5(17)

001lowast

CT29

(56)

11(44)

23(56)

18(45)

10(63)

31(48)

34(51)

6(46)

24(57)

7(24)

TT11(21)

10(40)

9(22)

14(35)

5(31)

18(28)

19(28)

4(31)

6(14

)17

(59)

C53

(51)

19(38)

01678

41(50)

34(43)

03496

12(38)

63(48)

03240

62(46)

12(46)

00566

48(57)

17(29)

000

12lowast

T51

(49)

31(62)

41(50)

46(58)

20(63)

67(52)

72(54)

14(54)

36(43)

41(71)

rs2032582

(c2677GgtTA)

GG

9(17)

4(16)

05655

6(15)

7(185)

03793

1(6)

12(18)

03311

12(18)

1(8)

04136

10(24)

3(8)

000

67lowast

GT

25(48)

11(44)

22(54)

17(435)

7(44)

32(49)

32(48)

6(46)

22(53)

17(44)

TT13

(25)

10(40)

9(22)

15(385)

7(44)

17(26)

20(30)

4(31)

6(14

)18

(46)

TA2(4)

0(0)

2(5)

0(0)

1(6)

1(2)

1(1)

1(8)

2(5)

0(0)

GA

3(6)

0(0)

2(5)

1(35)

03(5)

2(3)

1(8)

2(5)

1(3)

G46

(44)

19(38)

01985

36(44)

32(40)

03448

9(28)

59(45)

01642

58(43)

9(35)

00529

44(52)

24(31)

000

28lowast

T53

(51)

31(62)

42(51)

47(59)

22(69)

67(52)

73(54)

15(58)

36(43)

53(68)

A5(6)

0(0)

4(5)

1(1)

1(3)

4(3)

3(3)

2(8)

4(5)

1(1)

rs104564

2(c3435CgtT)

CC9(17)

4(16)

1000

8(20)

5(12)

04179

0(0)

13(20)

003

15lowast

12(18)

1(8)

08447

10(24)

3(8)

003

89lowast

CT23

(44)

11(44)

19(46)

16(39)

11(69)

24(37)

28(42)

6(46)

20(48)

15(38)

TT20

(38)

10(40)

14(34)

19(46)

5(31)

28(43)

27(40)

6(46)

12(29)

21(54)

C41

(39)

19(38)

1000

35(43)

26(33)

11977

11(34)

50(38)

08389

52(39)

8(31)

001

13lowast

40(48)

21(27)

000

92lowast

T63

(61)

31(62)

47(57)

54(68)

21(66)

80(62)

82(61)

18(69)

44(52)

57(73)

GLCC

I1

rs37972(c-1473TgtC)

CC16

(31)

11(44)

04931

13(32)

15(38)

08291

8(50)

20(31)

02289

24(36)

4(31)

1000

11(26)

17(44)

02726

CT26

(50)

11(44)

21(51)

20(50)

5(31)

35(54)

33(49)

7(54)

23(55)

17(44)

TT10

(19)

3(12)

7(17)

5(13)

3(19

)10

(15)

10(15)

2(15)

8(19

)5(13)

C58

(56)

33(66)

02938

47(57)

50(63)

0525

21(66)

75(58)

05473

81(60)

15(58)

1000

45(54)

51(65)

01506

T46

(44)

17(34)

35(43)

30(38)

11(34)

55(42)

53(40)

11(42)

39(46)

27(35)

rs37973(c-1106GgtA)

AA

14(27)

12(48)

0119

712

(29)

15(38)

06024

8(50)

19(29)

01861

22(33)

5(38)

08423

9(21)

18846)

00623

GA

26(50)

11(44)

21(51)

20(50)

5(31)

35(54)

33(49)

7(54)

24(57)

16(41)

GG

12(23)

2(8)

8(20)

5(13

3(19

)11(17)

12(18)

1(8)

9(21)

5(13)

A54

(52)

35(70)

003

77lowast

45(55)

50(63)

03427

21(66)

73(56)

04246

77(57)

17(65)

06321

42(50)

52(67)

00387

G50

(48)

15(30)

37(45)

30(38)

11(34)

57(44)

57(43)

9(35)

42(50)

26(33)

NR3

C1rs41423247

(c1184+6

46Cgt

G)

GG

20(38)

5(20)

001

73lowast

14(34)

11(28)

004

42lowast

5(31)

21(32)

05928

23(34)

2(15)

02363

16(38)

10(26)

00655

GC

17(33)

17(68)

14(34)

24(60)

6(38)

31(48)

31(46)

6(46)

14(33)

23(59)

CC15

(29)

3(12)

13(32)

5(13)

5(31)

13(20)

13(19

)5(38)

12(29)

6(15)

G57

(55)

27(54)

1000

42(51)

46(58)

04352

16(50)

73(56)

05571

77(57)

10(38)

03479

46(55)

43(55)

1000

C47

(45)

23(46)

40(49)

34(43)

16(50)

57(44)

57(43)

16(62)

38(45)

35(45)














GPC5





MDR1











217186 [12] 21218 [22]1123 [30]

GLCCI1


lowastOnly control

5 Conclusion




Competing Interests


References









































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of

















Table5Com

paris

onof

geno

type

andallelefre

quencies

ofglucocortic

oidmetabolism

gene

varia

ntsandselected

clinicalfeaturesGC


NR

norespon

seIS

immun

osup

pressiv

edrugs119901

values

lower

than

005

arem

arkedwithlowast

Gene

SNP

Genotype

Relap

ses

Frequent

relap

ser()

Age

ofon

set()

Respon

seto

GC

Treatm

ent

lt5gt5

119901No

Yes

119901lt3gt3

119901Normal

Slow

NR119901

OnlyGCs

IS119901

119899=52119899=25

119899=41119899=40

119899=16119899=65

119899=67119899=13

119899=42119899=39

MDR1

rs1128503

(c12

36Cgt

T)

CC12

(23)

4(16)

02330

9(22)

8(20)

04526

1(6)

16(25)

02863

14(21)

3(23)

1000

12(29)

5(17)

001lowast

CT29

(56)

11(44)

23(56)

18(45)

10(63)

31(48)

34(51)

6(46)

24(57)

7(24)

TT11(21)

10(40)

9(22)

14(35)

5(31)

18(28)

19(28)

4(31)

6(14

)17

(59)

C53

(51)

19(38)

01678

41(50)

34(43)

03496

12(38)

63(48)

03240

62(46)

12(46)

00566

48(57)

17(29)

000

12lowast

T51

(49)

31(62)

41(50)

46(58)

20(63)

67(52)

72(54)

14(54)

36(43)

41(71)

rs2032582

(c2677GgtTA)

GG

9(17)

4(16)

05655

6(15)

7(185)

03793

1(6)

12(18)

03311

12(18)

1(8)

04136

10(24)

3(8)

000

67lowast

GT

25(48)

11(44)

22(54)

17(435)

7(44)

32(49)

32(48)

6(46)

22(53)

17(44)

TT13

(25)

10(40)

9(22)

15(385)

7(44)

17(26)

20(30)

4(31)

6(14

)18

(46)

TA2(4)

0(0)

2(5)

0(0)

1(6)

1(2)

1(1)

1(8)

2(5)

0(0)

GA

3(6)

0(0)

2(5)

1(35)

03(5)

2(3)

1(8)

2(5)

1(3)

G46

(44)

19(38)

01985

36(44)

32(40)

03448

9(28)

59(45)

01642

58(43)

9(35)

00529

44(52)

24(31)

000

28lowast

T53

(51)

31(62)

42(51)

47(59)

22(69)

67(52)

73(54)

15(58)

36(43)

53(68)

A5(6)

0(0)

4(5)

1(1)

1(3)

4(3)

3(3)

2(8)

4(5)

1(1)

rs104564

2(c3435CgtT)

CC9(17)

4(16)

1000

8(20)

5(12)

04179

0(0)

13(20)

003

15lowast

12(18)

1(8)

08447

10(24)

3(8)

003

89lowast

CT23

(44)

11(44)

19(46)

16(39)

11(69)

24(37)

28(42)

6(46)

20(48)

15(38)

TT20

(38)

10(40)

14(34)

19(46)

5(31)

28(43)

27(40)

6(46)

12(29)

21(54)

C41

(39)

19(38)

1000

35(43)

26(33)

11977

11(34)

50(38)

08389

52(39)

8(31)

001

13lowast

40(48)

21(27)

000

92lowast

T63

(61)

31(62)

47(57)

54(68)

21(66)

80(62)

82(61)

18(69)

44(52)

57(73)

GLCC

I1

rs37972(c-1473TgtC)

CC16

(31)

11(44)

04931

13(32)

15(38)

08291

8(50)

20(31)

02289

24(36)

4(31)

1000

11(26)

17(44)

02726

CT26

(50)

11(44)

21(51)

20(50)

5(31)

35(54)

33(49)

7(54)

23(55)

17(44)

TT10

(19)

3(12)

7(17)

5(13)

3(19

)10

(15)

10(15)

2(15)

8(19

)5(13)

C58

(56)

33(66)

02938

47(57)

50(63)

0525

21(66)

75(58)

05473

81(60)

15(58)

1000

45(54)

51(65)

01506

T46

(44)

17(34)

35(43)

30(38)

11(34)

55(42)

53(40)

11(42)

39(46)

27(35)

rs37973(c-1106GgtA)

AA

14(27)

12(48)

0119

712

(29)

15(38)

06024

8(50)

19(29)

01861

22(33)

5(38)

08423

9(21)

18846)

00623

GA

26(50)

11(44)

21(51)

20(50)

5(31)

35(54)

33(49)

7(54)

24(57)

16(41)

GG

12(23)

2(8)

8(20)

5(13

3(19

)11(17)

12(18)

1(8)

9(21)

5(13)

A54

(52)

35(70)

003

77lowast

45(55)

50(63)

03427

21(66)

73(56)

04246

77(57)

17(65)

06321

42(50)

52(67)

00387

G50

(48)

15(30)

37(45)

30(38)

11(34)

57(44)

57(43)

9(35)

42(50)

26(33)

NR3

C1rs41423247

(c1184+6

46Cgt

G)

GG

20(38)

5(20)

001

73lowast

14(34)

11(28)

004

42lowast

5(31)

21(32)

05928

23(34)

2(15)

02363

16(38)

10(26)

00655

GC

17(33)

17(68)

14(34)

24(60)

6(38)

31(48)

31(46)

6(46)

14(33)

23(59)

CC15

(29)

3(12)

13(32)

5(13)

5(31)

13(20)

13(19

)5(38)

12(29)

6(15)

G57

(55)

27(54)

1000

42(51)

46(58)

04352

16(50)

73(56)

05571

77(57)

10(38)

03479

46(55)

43(55)

1000

C47

(45)

23(46)

40(49)

34(43)

16(50)

57(44)

57(43)

16(62)

38(45)

35(45)














GPC5





MDR1











217186 [12] 21218 [22]1123 [30]

GLCCI1


lowastOnly control

5 Conclusion




Competing Interests


References









































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of





























GPC5





MDR1











217186 [12] 21218 [22]1123 [30]

GLCCI1


lowastOnly control

5 Conclusion




Competing Interests


References









































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of

















Competing Interests


References









































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of


























of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of
















research article single nucleotide polymorphisms in ...research article single nucleotide...

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