mi-risk product descriptionepsilon2/epsilon3/epsilon4 genotype in modulating apolipoprotein e...

MIRISKMYOCARDIALINFARCTIONTEST

PRODUCTDESCRIPTION

PERSONALGENOMICSSRLStradaLeGrazie15I-37134VeronaP.IvaeCod.Fiscale04024620231Tel.(+39)[email protected]

thetest

The MI RISK kit is an innovative and unique tool for the personalized predispositiondetectionandpreventionofdangerousmedicalconditions.

MIRISKhelps thepatient to carryout preventivebehaviorsmany years if not decadesbefore the occurrence of a possible life threatening health condition, obtaining aconsiderableadvantageonhis/herfuturelifequality.

TheMIRISKanalysiscalculatesthechancesofincurringinacardiovasculareventoveraspecific time period taking into consideration both standard cardiovascular diagnosticparametersandthepersonalizedgeneticpredispositionrisk.

Everyyearcardiovasculardiseaseskillover4.3millionpeopleinEuropeandcausethe48%ofthetotalamountofdeaths(54%inwomen,43%inmen).Thosediseasesarethefirstcause of death, themost frequent causeof admitting to hospital andoneof themostimportantcausesofinvalidity.

Theriskfactors(thetraitswhich,ifpresentinapersonorpopulation,indicatethegraterchances to incur in that illness)of thosediseases are verywell known. Epidemiologicalstudiesinthelastyearshaveshownthattheriskisreversibleanditispossibletoreduceorpostponetheriskofincurringincardiovasculareventsviareducingtheriskfactors.


riskfactorsandmyocardialinfarction

Duringthelastyearseveralexhaustivestudies,bothnationwideandworldwide,revealedhow the geneticmakeup influences cardiovascular risk. Everyonehas a specific geneticasset,which is unique andnotmodifiable, that renderhim/her liable to cardiovasculardiseases.TheMIRISKkitcanquantifythis“basicgeneticrisk”,puttingtogetherworldwideknowledgeandstate-of-the-artgenetictechnology.

Apersoncantakeadvantageofknowingifhe/shehasahighercardiovascularrisk,actinginordertoreduceotherriskfactorwithahealthierwayoflifeandreferringtomedicalhelpto know which strategies would be best to reduce the risk of a cardiovascular event.Examiningmutations in theDNAand relating them to the lifestylepermit to compileacombinedevaluationofriskandsuggestthebeststrategies.

Traditional risk represents a statistic evaluation of chances to incur in cardiovascularevents in the next 10 years assuming the current conditions will remain identical(cholesterol levels, blood pressure, smoke, etc.) This kind of risk is calculated withtraditionalparametersaccordingwiththeItalianSuperiorInstituteofHealthcare.

Genetic risk represents the individual predisposition to diseases depending on theinformationintheDNA.ItisknownthatspecificmutationsinsomegenesintheDNAhavea critical role in developing cardiovascular diseases. To realize an efficient preventionagainstthoseillnessesitisessentialtoidentifythegeneticriskfactorsthatcouldimprovechancestodevelopthem.

TheDNAtestdoesnotsetonceandforallifapersonwilldevelopadiseaseforsure,butgivesgreatadviceabouthis/hergeneticpredisposition,soonecanimplementpersonalizedprecautionarymeasurestoimprovechancesofgoodhealth.

The total amount of traditional and genetic risks is elaborated by Personal Genomics’medical teamthrougha specificalgorithmwhichallows themedical teamtodevelopacombinedriskanalysisthatcontainsallthoseparameters.

Cardiovascular diseases andmyocardial infarction in particular are nowadays the firstcauseofdeathintheworld.Notallthosedeathsarecausedbycommonriskfactorssuchassmokinghabits,diabetes,hypertension,highcholesterolrates,obesityetc.Ithasbeen


demonstratedthatthegeneticpredispositionhasacriticalroleinthesediseases.RecentGenome-Wide Association Studies (GWAS) allowed the identification of crucial geneticmarkersthatgreatlyimprovethepredictivepowerofthetestfortheriskassessmentofAcuteMyocardialInfarction.

Predisposition genetic markers are used in combination with individual informationregardingtraditionalriskfactorsforthecalculationofthepersonalizedrisk.(GirelliD.etal,SeminarsinThrombosisandHemostasis2009;ViselA.etal.,Nature2010).

testingprocedure

MIRISK testingprocedurestartswithsample takingandanamnesiscollection.PersonalGenomictakescareoftheDNAextractionpriorthebeginningoftheSNPsanalysisprocess.Therisklevelprofileisassessedandreportedonthefinaltestresults.

Sampleandanamnesiscollection

DispatchtoPersonalGenomics

Reception,storageandDNAextraction

SNPsanalysisprocessRisklevelprofilingDispatchoutcomes


kitusageThekitisverysimpletouse:itconsistsofasmallswabthatthecustomercandirectlyusetocollectasalivasamplesimplypassingitinhisownmouth.PersonalGenomicswillthenextracttheDNAfromthesalivasampleprovidedbythecustomer.Asimplequestionnairewillbeusedtocollecttheinformationaboutthetraditionalriskfactorsthatwillbeusedtoobtainananamnesisthatcomplementsthegeneticinformationprovidedwiththemedicalreport.

SNPsanalysisThegeneticanalyzerevaluatesthepresenceofaseriesofgeneticpolymorphisms(SNPs)associatedwith the AcuteMyocardial Infarction’s risk. The geneticmarkers consideredwereselectedonthewholegenomebasedontheirstatisticalpredictivevalue,whichwasdemonstratedinrecentscientificpublications(ViselA.etal.,Nature2010andSchunkertH.etal.,NatureGenetics2011).


kitresultsTheresultsofthegeneticanalysisprovideageneticriskscorespecificforeachindividual.Thetesttakesintoaccountboththe“damaging”andthe“protective”geneticallelesfortheglobalcardiovascularriskandtheirrelativeeffectbasedonGenomeWideAssociationStudies (GWAS). The genetic information analyzedwith the kit is then integratedwithgeneralmedical information regardingeach individual’s lifestyleand the traditional riskfactorsconsideredbycardiologists (bloodpressure,cholesterol,smokinghabits,weight,age,etc.)

The final result consists in a risk profile that assesses thepersonal probability of acuteMyocardial Infarctoveraspecifictimeframe.Thetestcanpointoutpossiblebadhabitsand/ormodifiablebehaviorsfortheimprovementoftheperson’soverallhealthandthecardiovascular apparatus efficiency through specific disease prevention actions. Aspecializedclinicianandageneticistcertifythemedicalreportprovided.

Thecombinedriskanalysisofmyocardialinfarctiongivesaccurateinformationbothontherisk extent to incur in heart pathologies, and on which preventive measures adopt toreduce that risk. Anyway Personal Genomics’ business mission is to offer the mostcomplete service to its clients; inorder todo so, it instituted someReferenceCenters,whichareabletofollowtheclientinordertogivemoresupportandcounselingaboutthetestresults,incollaborationwithcardiovascularspecialistsofexcellence.

testingtargetMIRISKisintendedforaverywidesetofpeopleandaverylargeagegroupthatincludesallthosepeopleawarethatsomeofthepeculiarcharacteristicsofnowadays’life,suchadeskboundjob,anon-balanceddiet,stressandhypertension,canworsenageneticsystemwhichmightbepotentiallyalreadypronetothedevelopmentofcardiovasculardiseases.Suchariskawarenesshelpspreventingtheactualdevelopmentofthedisease,andgivesadvices on which habits to change in order to improve the lifestyle or which medicalpreventionactionstoconsider.

othercharacteristics

MIRISKisnoninvasive.TheDNAforthetestisextractedfromthesalivacollectedthroughasimpleswab.Itisaneasyandabsolutelynon-invasivemethod.

MIRISKisone-shot.Resultsarevalidfortheentirelife:thegeneticvariantsanalyzedarepresent ineachperson’sDNAanddonotchangeduringthe lifetimeunlikebiochemicalparametersassessedinstandardmedicalexams.TheMIRiskresultdefinesyourgeneticprofileandpredispositiontomyocardialinfarctionjustonceinyourlifetime.

MIRISKisdecisive.Oncethetestisperformed,theriskisaccuratelycalculatedusinganalgorithmthatcombinesgeneticvariations(SNPs)andtraditionalriskfactors.Amedicaldoctorevaluatesthecalculatedriskandadjustthemedicalreportontheindividualcasesuggesting specific medical analysis (ECG, etc.), the evaluation of drug preventiveregimentsorspecificbehaviorchangesinordertolowertherisk.


thecompany

Personal Genomics is a spin-off of the Functional Genomics Center of the prestigiousUniversityofVerona.Ourmissionistoofferservices,productsandsolutionswithhighlyinnovative technological content intended for the Precision Medicine, diagnostics andgenomicsfields.

ItwasbornthankstotheextraordinaryexperienceofthreegreatprofessionalsinGeneticsandCardiovascularMedicine,worldwideacknowledged:professorMassimoDelledonne,professorOlivieroOlivieriandprofessorDomenicoGirelli.

PersonalGenomicsoffersquiteanumberofproductsatthestateoftheartandseveralservicesingenetics.Duringthelastyearsthelatestdiscoveriesinthegeneticenvironmentuptothecompletesequencingofthehumangenome,havebroughtagreatamountofinformation about the genetic variability betweenhumanbeings; the great progress ingenetic research brought a revolution in the concept itself of Medicine, bringing newperspectives in prevention, diagnosis and treatment of diseases. These discoveries andtheirapplicationshavebroughtinformationunavailablebeforeandthatarenowcrucialindiagnosisandpreventionofdiseases.

Personal Genomics promotes this innovative concept of Precision Medicine, i.e. anapproachindiagnosisandtreatmentofillnessespersonalizedforeverysinglepersononhis/hergeneticmakeupbasis.


references

o TheMIGENConsortium.Genome-wideassociationofearly-onsetmyocardialinfarctionwithsinglenucleotidepolymorphismsandcopynumbervariants.NatGenet2009;41:334-41http://www.ncbi.nlm.nih.gov/pubmed/19198609

o SchunkertHetal.CARDIoGRAM.Large-scaleassociationanalysisidentifies13newsusceptibilitylociforcoronaryarterydisease.NatGenet2011;43:333-338http://www.ncbi.nlm.nih.gov/pubmed/21378990

o GirelliD,MartinelliN,PeyvandiF,OlivieriO.Geneticarchitectureofcoronaryarterydiseaseinthegenome-wideera:Implicationsfortheemerging“Goldendozen”loci.SeminThrombHemost.2009;35:671-82.http://www.ncbi.nlm.nih.gov/pubmed/20013534

o MartinelliNetal.Combinedeffectofhemostaticgenepolymorphismsandtheriskofmyocardialinfarctioninpatientswithadvancedcoronaryatherosclerosis.PLoSOne.2008Feb6;3(2):e1523.http://www.ncbi.nlm.nih.gov/pubmed/18253477

o MartinelliN.etal.PolymorphismsatLDLRlocusmaybeassociatedwithcoronaryarterydiseasethroughmodulationofcoagulationfactorVIIIactivityandindependentlyfromlipidprofile.Blood.2010Dec16;116(25):5688-97.http://www.ncbi.nlm.nih.gov/pubmed/20810930

o MartinelliN,OlivieriO,etal.AdditiveeffectofLRP8/APOER2R952QvarianttoAPOEepsilon2/epsilon3/epsilon4genotypeinmodulatingapolipoproteinEconcentrationandtheriskofmyocardialinfarction:acase-controlstudy.BMCMedGenet.2009May13;10:41.http://www.ncbi.nlm.nih.gov/pubmed/19439088

o OlivieriO.etal.ApolipoproteinC-IIIpredictscardiovascularmortalityinseverecoronaryarterydiseaseandisassociatedwithanenhancedplasmathrombingeneration.JournalofThrombosis&Haemostasis2010;8(3):463-471.http://www.ncbi.nlm.nih.gov/pubmed/20002542

o BrautbarA,etal.Impactofaddingasinglealleleinthe9p21locustotraditionalriskfactorsonreclassificationofcoronaryheartdiseaseriskandimplicationsforlipid-modifyingtherapyintheAtherosclerosisRiskinCommunitiesstudy.CircCardiovascGenet.2009Jun;2(3):279-85.http://www.ncbi.nlm.nih.gov/pubmed/20031596


o KathiresanS,etal.Polymorphismsassociatedwithcholesterolandriskofcardiovascularevents.NEnglJMed.2008Mar20;358(12):1240-9.http://www.nejm.org/doi/pdf/10.1056/NEJMoa0706728

o GudbjartssonDFetal.Sequencevariantsaffectingeosinophilnumbersassociatewithasthmaandmyocardialinfarction.NatGenet.2009Mar;41(3):342-7.http://www.ncbi.nlm.nih.gov/pubmed/19198610

o GretasdottirSetal.Genome-wideassociationstudyidentifiesasequencevariantwithintheDAB2IPgeneconferringsusceptibilitytoabdominalaorticaneurysmNatGenet.2010Aug;42(8):692-7.Epub2010Jul11.http://www.ncbi.nlm.nih.gov/pubmed/20622881

o ReillyMPetal.IdentificationofADAMTS7asanovellocusforcoronaryatherosclerosisandassociationofABOwithmyocardialinfarctioninthepresenceofcoronaryatherosclerosis:twogenome-wideassociationstudies.Lancet.2011Jan29;377(9763):383-92.http://www.ncbi.nlm.nih.gov/pubmed/21239051

o IsaacsA.,WillemsS.M.etal.RiskScoresofCommonGeneticVariantsforLipidLevelsInfluenceAtherosclerosisandIncidentCoronaryHeartDisease,ArteriosclerThrombVascBiol.2013Sep;33(9):2233-9.doi:10.1161/ATVBAHA.113.301236.Epub2013Jun13.http://www.ncbi.nlm.nih.gov/pubmed/23766260

o TikkanenE.etal.GeneticRiskPredictionanda2-StageRiskScreeningStrategyforCoronaryHeartDisease;ArteriosclerThrombVascBiol.2013Sep;33(9):2261-6.doi:10.1161/ATVBAHA.112.301120.Epub2013Apr18http://www.ncbi.nlm.nih.gov/pubmed/23599444

o GannaA.etal.MultilocusGeneticRiskScoresforCoronaryHeartDiseasePrediction;ArteriosclerThrombVascBiol.2013Sep;33(9):2267-2272.Epub2013May16.http://www.ncbi.nlm.nih.gov/pubmed/23685553

o ThanassoulisG.etal.GenomicMedicineforImprovedPredictionandPrimordialPreventionofCardiovascularDisease;ArteriosclerThrombVascBiol.2013Sep;33(9):2049-50.doi:10.1161/ATVBAHA.113.301814.http://www.ncbi.nlm.nih.gov/pubmed/23946465

o VoightB.F.,PelosoG.M.etal.PlasmaHDLcholesterolandriskofmyocardialinfarction:amendelianrandomisationstudy;Lancet.2012Aug11;380(9841):572-80.doi:10.1016/S0140-6736(12)60312-2.Epub2012May17http://www.ncbi.nlm.nih.gov/pubmed/22607825

mi-risk product descriptionepsilon2/epsilon3/epsilon4 genotype in modulating apolipoprotein e...

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