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

Abstract

OBJECTIVE— To determine whether the peroxisome proliferator–activated receptor (PPAR)- Pro12ala polymorphism modulates susceptibility to diabetes in South Asians. RESEARCH DESIGNANDMETHODS— South Asians (n697) and Caucasians (n 457) living in Dallas/Forth Worth, Texas, and South Asians living in Chennai, India (n1,619), were enrolled for this study. PPAR- Pro12Ala was determined using restriction fragment– length polymorphism. Insulin responsiveness to an oral glucose tolerance test (OGTT) was measured in nondiabetic subjects. RESULTS— The Caucasian diabetic subjects had significantly lower prevalence of PPAR- 12Ala when compared with the Caucasian nondiabetic subjects (20 vs. 9%, P 0.006). However, there were no significant differences between diabetic and nondiabetic subjects with reference to the Pro12Ala polymorphism among the South Asians living in Dallas (20 vs. 23%) and in India (19 vs. 19.3%). Although Caucasians carrying PPAR- Pro12Ala had lower plasma insulin levels at 2 h of OGTT than the wild-type (Pro/Pro) carriers (7668 and 5433 U/ml, respectively, P0.01), no differences in either fasting or 2-h plasma insulin concentrations were found between South Asians carrying the PPAR- Pro12Ala polymorphism and those with the wild-type genotype at either Chennai or Dallas. CONCLUSIONS— Although further replication studies are necessary to test the validity of the described genotype-phenotype relationship, our study supports the hypothesis that the PPAR- Pro12Ala polymorphism is protective against diabetes in Caucasians but not in South Asians.