Evidence for an association with type 2 diabetes mellitus at the PPARG locus in a South Indian population

Vimaleswaran, Karani S and Radha, Venkatesan and Jayapriya, Munuguru Gopal and Ghosh, Saurabh and Majumder, Partha P and Rao, Sathyanarayana MR and Mohan, Viswanathan (2010) Evidence for an association with type 2 diabetes mellitus at the PPARG locus in a South Indian population. In: Metabolism, 59 (4). 457 -462.

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Abstract

Peroxisome proliferator activated receptor-gamma 2 (PPARG2) is a nuclear hormone receptor of ligand-dependent ranscription factor involved in adipogenesis and a molecular target of the insulin sensitizers thiazolidinediones. We addressed the question of whether the 3 variants (-1279G/A, Pro12Ala, and His478His) in the PPARG2 gene are associated with type 2 diabetes mellitus and its related traits in a South Indian population. The study subjects (1000 type 2 diabetes mellitus and 1000 normal glucose-tolerant subjects) were chosen randomly from the Chennai Urban Rural Epidemiology Study, an ongoing population-based study in southern India. The variants were screened by single-stranded conformational variant, direct sequencing, and restriction fragment length polymorphism. Linkage disequilibrium was estimated from the estimates of haplotypic frequencies. The -1279G/A, Pro12Ala, and His478His variants of the PPARG2 gene were not associated with type 2 diabetes mellitus. However, the 2-loci analyses showed that, in the presence of Pro/Pro genotype of the Pro12Ala variant, the -1279G/A promoter variant showed increased susceptibility to type 2 diabetes mellitus (odds ratio, 2.092; 95% confidence interval, 1.22-3.59; P = .008), whereas in the presence of 12Ala allele, the -1279G/A showed a protective effect against type 2 diabetes mellitus (odds ratio, 0.270; 95% confidence interval, 0.15-0.49; P < .0001). The 3-loci haplotype analysis showed that the A-Ala-T (-1279G/A-Pro12Ala-His478His) haplotype was associated with a reduced risk of type 2 diabetes mellitus (P < .0001). Although our data indicate that the PPARG2 gene variants, independently, have no association with type 2 diabetes mellitus, the 2-loci genotype analysis involving -1279G/A and Pro12Ala variants and the 3-loci haplotype analysis have shown a significant association with type 2 diabetes mellitus in this South Indian population. (C) 2010 Elsevier Inc. All rights reserved.

Item Type:	Journal Article
Publication:	Metabolism
Publisher:	Elsevier Science
Additional Information:	Copyright of this article belongs to Elsevier Science.
Keywords:	Coronary-heart-disease; gamma gene; insulin-resistance; glucose-tolerance; c1431t variants; asian indians; pro12ala; polymorphism; obesity; susceptibility
Department/Centre:	Division of Biological Sciences > Biochemistry
Date Deposited:	23 Apr 2010 07:43
Last Modified:	19 Sep 2010 06:00
URI:	http://eprints.iisc.ac.in/id/eprint/27194

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