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, PHD1,
- Karani S. Vimaleswaran, MSC1,
- Hunsur Narayan S. Babu, MSC2,
- Nicola Abate, MD3,
- Manisha Chandalia, MD3,
- Pankaj Satija, MD3,
- Scott M. Grundy, MD, PHD3,
- Saurabh Ghosh, PHD4,
- Partha P. Majumder, PHD4,
- Raj Deepa, PHD1,
- Sathyanarayana M.R. Rao, PHD2 and
- Viswanathan Mohan, MD1
- 1Dr. Mohan’s Diabetes Specialities Centre, Madras Diabetes Research Foundation, Gopalapuram, Chennai, India;
- 2Department of Biochemistry, Indian Institute of Science, Jawaharal Nehru Centre for Advanced Scientific Research, Bangalore, India;
- 3Department of Internal Medicine, Centre for Human Nutrition, University of Texas Southwestern Medical Center, Dallas, Texas;
- 4Indian Statistical Institute, Calcutta, India
- Address correspondence reprint requests to V. Radha, Department of Molecular Genetics, Madras Diabetes Research FoundationDr. Mohan’s Diabetes Specialties Centre, No. 4, Conran Smith Road, Gopalapuram, Chennai-86, India. E-mail: radhav{at}yahoo.com. Or to Nicola Abate, UT Southwestern Medical Center, 6011 Harry Hines Blvd., Dallas, TX 75390-9169. E-mail: nicola.abate{at}utsouthwestern.edu
Abstract
OBJECTIVE—To determine whether the peroxisome proliferator–activated receptor (PPAR)-γ Pro12ala polymorphism modulates susceptibility to diabetes in South Asians.
RESEARCH DESIGN AND METHODS—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.
- CURES, Chennai Urban Rural Epidemiology Study
- HOMA-IR, homeostasis model assessment for insulin resistance
- OGTT, oral glucose tolerance test
- PPAR, peroxisome proliferator–activated receptor
Footnotes
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A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.
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The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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- Accepted February 7, 2006.
- Received August 8, 2005.
- DIABETES CARE
