Role of Genetic Polymorphism Peroxisome Proliferator-Activated Receptor- 2 Pro12Ala on Ethnic Susceptibility to Diabetes in South-Asian and Caucasian Subjects: Evidence for Diabetes in South-Asian

摘要

OBJECTIVE— To determine whether the peroxisome proliferator–activated receptorud(PPAR)- Pro12ala polymorphism modulates susceptibility to diabetes in South Asians.udRESEARCH DESIGNANDMETHODS— South Asians (n697) and Caucasians (nud457) living in Dallas/Forth Worth, Texas, and South Asians living in Chennai, India (n1,619),udwere enrolled for this study. PPAR- Pro12Ala was determined using restriction fragment–udlength polymorphism. Insulin responsiveness to an oral glucose tolerance test (OGTT) wasudmeasured in nondiabetic subjects.udRESULTS— The Caucasian diabetic subjects had significantly lower prevalence of PPAR-ud12Ala when compared with the Caucasian nondiabetic subjects (20 vs. 9%, P 0.006). However,udthere were no significant differences between diabetic and nondiabetic subjects with referenceudto the Pro12Ala polymorphism among the South Asians living in Dallas (20 vs. 23%) andudin India (19 vs. 19.3%). Although Caucasians carrying PPAR- Pro12Ala had lower plasmaudinsulin levels at 2 h of OGTT than the wild-type (Pro/Pro) carriers (7668 and 5433 U/ml,udrespectively, P0.01), no differences in either fasting or 2-h plasma insulin concentrations wereudfound between South Asians carrying the PPAR- Pro12Ala polymorphism and those with theudwild-type genotype at either Chennai or Dallas.udCONCLUSIONS— Although further replication studies are necessary to test the validity ofudthe described genotype-phenotype relationship, our study supports the hypothesis that theudPPAR- Pro12Ala polymorphism is protective against diabetes in Caucasians but not in SouthudAsians.