Role of genetic polymorphism peroxisome proliferator-activated receptor-γ2 Pro12Ala on ethnic susceptibility to diabetes in South-Asian and Caucasian subjects: Evidence for heterogeneity

Venkatesan Radha, Karani S. Vimaleswaran, Hunsur Narayan S Babu, Nicola Abate, Manisha Chandalia, Pankaj Satija, Scott M Grundy, Saurabh Ghosh, Partha P. Majumder, Raj Deepa, Sathyanarayana M R Rao, Viswanathan Mohan

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99 Scopus citations

Abstract

OBJECTIVE - To determine whether the peroxisome proliferator-activated receptor (PPAR)-γ Pro12ala polymorphism modulates susceptibility to diabetes in South Asians. RESEARCH DESIGNANDMETHODS - South Asians (n = 697) and Caucasians (n = 457) living in Dallas/Forth Worth, Texas, and South Asians living in Chennai, India (n = 1,619), were enrolled for this study. PPAR-γ 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-γ 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-γ Pro12Ala had lower plasma insulin levels at 2 h of OGTT than the wild-type (Pro/Pro) carriers (76 ± 68 and 54 ± 33 μU/ml, respectively, P = 0.01), no differences in either fasting or 2-h plasma insulin concentrations were found between South Asians carrying the PPAR-γ 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-γ Pro12Ala polymorphism is protective against diabetes in Caucasians but not in South Asians.

Original languageEnglish (US)
Pages (from-to)1046-1051
Number of pages6
JournalDiabetes care
Volume29
Issue number5
DOIs
StatePublished - 2006

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Advanced and Specialized Nursing

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