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GeneticsofDiabetesJanDorman,PhDUniversityofPittsburghSchoolofNursing
Type1Diabetes(T1D)
InsulinisnolongerproducedLeadstohyperglycemia,ketoacidosisandpotentiallydeathifnottreatedwithinsulinCausedbythedestructionofthepancreaticbetacells01MaintainingnearnormallevelsofbloodglucoseAvoidanceoflong-termcomplicationsTreatmentgoalsforT1D02Type1Diabetes
2ndmostcommonchronicchildhooddiseasePeakageatonsetisaroundpubertyButT1DcanoccuratanyageIncidenceisincreasingworldwideby~3%peryearRelatedtoincreaseinT2D?Type1Diabetes
T1DIncidenceWorldwide
ImportanceofEnvironmentalRiskFactorsinT1DSeasonalityatdiagnosisMigrantsassumeriskofhostcountryRiskfactorsfromcase-controlstudiesInfant/childhooddietViruses–exposuresasearlyasinuteroHormonesStressImprovedhygieneVitaminD
ImportanceofGeneticRiskFactorsinT1DConcordanceinidenticaltwinsgreaterinMZversusDZtwins15-foldincreasedriskfor1stdegreerelativesRiskis~6%throughage30yearsRiskincreasesinpresenceofsusceptibilitygenes
MHCRegion–Chromosome6p21
PredispositiontoT1DisBetterDeterminedbyHaplotypesDRB1-DQB1haplotypesmoreaccuratelydetermineT1DriskTestingforbothgenesismoreexpensiveMostscreeningisbasedonlyonDQA1-DQB1HighriskT1DhaplotypesDQA1*0501-DQB1*0201DQA1*0301-DQB1*0302010302
RelativeIncreaseinT1DRiskbyNumberofHighRiskHaplotypesNumberofHighRiskDQA1-DQB1haplotypesEthnicityTwoOneCaucasians164AfricanAmericans457Asians114
AbsoluteT1DRisk(toage30)byNumberofHighRiskHaplotypesNumberofHighRiskDQA1-DQB1HaplotypesEthnicityTwoOneZeroCaucasians2.6%0.7%0.2%AfricanAmericans3.1%0.5%0.1%Asians0.2%0.1%0.02%
AbsoluteT1DRiskforSiblingsofAffectedIndividualsNumberofHighRiskDQA1-DQB1HaplotypesTwoOneZeroRiskofdevelopingT1D25%8.3%1%
GenomeScreensforT1DIDDM16p21IDDM132q34-q35IDDM211p15IDDM156q21IDDM315q26IDDM1710q25IDDM411q13IDDM185q31-q33IDDM56q25-q27PTP
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