糖尿病的遗传学.pptx

Genetics of DiabetesJan Dorman, PhD University of Pittsburgh School of Nursing mailto:jsd@jsd@Type 1 Diabetes (T1D)Type 1 DiabetesCaused by the destruction of thepancreatic beta cells– Insulin is no longer produced– Leads to hyperglycemia, ketoacidosis and potentially death if not treated with insulinTreatment goals for T1DMaintaining near normal levels of blood glucoseAvoidance of long-term complicationsType 1 Diabetes2nd most common chronic childhood diseasePeak age at onset is around pubertyBut T1D can occur at any ageIncidence is increasing worldwide by ~3% per yearRelated to increase in T2D?T1D Incidence WorldwideImportance of Environmental Risk Factors in T1DSeasonality at diagnosisMigrants assume risk of host countryRisk factors from case-control studiesInfant/childhood dietViruses – exposures as early as in uteroHormonesStressImproved hygieneVitamin DImportance of Genetic Risk Factors in T1DConcordance in identical twins greater in MZ versus DZ twins15-fold increased risk for 1st degree relativesRisk is ~6% through age 30 yearsRisk increases in presence of susceptibility genesMHC Region – Chromosome 6p21Predisposition to T1D is Better Determined by HaplotypesDRB1-DQB1 haplotypes more accurately determine T1D riskTesting for both genes is more expensiveMost screening is based only on DQA1-DQB1High risk T1D haplotypesDQA1*0501-DQB1*0201DQA1*0301-DQB1*0302Relative Increase in T1D Risk by Number of High Risk HaplotypesNumber of High Risk DQA1-DQB1 haplotypesEthnicityTwoOneCaucasians164African Americans457Asians114Absolute T1D Risk (to age 30) by Number of High Risk HaplotypesNumber of High RiskDQA1-DQB1 HaplotypesEthnicityTwoOneZeroCaucasians2.6%0.7%0.2%African Americans3.1%0.5%0.1%Asians0.2%0.1%0.02%Absolute T1D Risk for Siblings of Affected IndividualsNumber of High Risk DQA1-DQB1 HaplotypesTwoOneZeroRisk of developing T1D25%8.3%1%Genome Screens for T1DIDDM16p21IDDM132q34-q35IDDM211p15IDDM156q21IDDM315q26IDDM1710q25IDDM411q13IDDM185q31-q33IDDM56q25-q27PTPN221p