tumor necrosis factor-a haplotype

8/6/2019 Tumor Necrosis Factor-A Haplotype

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TUMOR NECROSIS FACTOR-LPHA

HAPLOTYPEIS STRONGLY ASSOCIATED

WITH BONE MINERAL DENSITY

IN PATIENTS WITH CROHN¶S DISEASE

Naomi Lee,* Elizabeth Fowler,� Susan Mason,Â Douglas Lincoln,§ Dennis RTaaffe* and

Graham Radford-Smith

DIPRESENTASIKAN OLEH

dr. ANANTA



BACKGROUND

CROHN·S DESEASE

INFLAMATORY

PROSSES

GENETIC

SUSCEPTIBILITY

MALABSORPTION CORTICOSTEROID

TREATMENT

DECREASE

BONE MINERAL DENSITY

INCREASE

MOBIDITY OF DESEASE



BACKGROUND

CROHN·S

DESEASE

DIFFICULT TOQUANTIFY AND

COMPARE FROM

STUDY TO STUDY

MOLECULAR BASIS

OF COMPLEX

DISORDERS

NOD2/CARD15

CL1A1 gene

TNF haplotype genes

DECREASE

BONE MINERAL

DENSITY

CLINICAL

VARIABLES



METHODS

304 patientsCROHN·S DESEASE

GENOTYPINGTNF CC and TNF GT

haplotype

Include: radiologic, hitologic,

endoscopic assesement

Exclude : medical condition that may

alter bone metabolism (renal or hepatic

desease, thyrotocsicosis,hyperparathiroidism,etc

STATISTICS ANALIZED

Pearson·s correlation coefficients

linear regression models (and t-tests)

analysis of variance (anova)

BONE

DENSITOMETRY



RESULTS

Individuals with normal BMD both at the hip and spinewere significantly more likely to inherit the high-TNF CC

genotype (P = 0.002) and had a strong negative association

with the low-TNF GT haplotype (P = 0.002)

The figures for spinal BMD alone were very similar, with

significant associations betweennormal spine BMD and the

CC genotype (P = 0.003), and the strong negative

association with a GT haplotype (P = 0.005)



RESULTS



DISCUSION

´ Crohn·s desease is a cronic inflamatory desease.

´ A number of other studies, including measurement of circulating TNF-a in cronic inflamatory , have suggested animportant role for TNF- as a skeletal catabolic agent.

´ The Problem of difficulties in studying circulating andtissue cytokines (TNF-) becouse of their very short half-life.

´ genetically determined variation in the concentration of

TNF-a may be a more reliable method to determinewhether this cytokine plays a role in bone metabolism inthe long term



DISCUSION

´ Present study determining a genetic association

between the TNF-a gene and bone loss by

incorporating both genotype and haplotype analysis.

´ There is strong correlation between these analyses

both for overall BMD

´ True association in the present study is between BMD

and gene that is in linkage disequilibrium with the

reported TNF-a genotypes and haplotype at 6p21



DISCUSION

´ Other stdudy demonstrated a significantly reduced

fracture risk in patients who had undergone bowel

surgery.

´ Removal of the inflamed segment may allowtemporary relief from pro-inflammatory cytokines such

as TNF that play a key role in bone resorption

´ Crohn·s Desese patient with high TNF-a genotypes

and haplotype at 6p21 has more circulatory cytokines

such as TNF . .



DISCUSION

´ The temporary reduction in intestinal inflammation

and associated reduction in steroid usage seen with

intestinal resection may temporarily prevent the

abnormal bone metabolism observed in patientswithout previous resection and in those with greater

duration since resection

´ More radical treatment to remove inflamatory segmen

in patient that has high TNF-a genotypes and

haplotype at 6p21 could reduce complication

decrease bone mineral density.

tumor necrosis factor-a haplotype

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