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

Vimaleswaran, K. S., Radha, V., Jayapriya, M. G., Ghosh, S., Majumder, P. P., Rao, M. R. S. and Mohan, V. (2010) Evidence for an association with type 2 diabetes mellitus at the PPARG locus in a South Indian population. Metabolism: Clinical and Experimental, 59 (4). pp. 457-462. ISSN 0026-0495

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To link to this item DOI: 10.1016/j.metabol.2009.07.034

Abstract/Summary

Peroxisome proliferator-activated receptor-gamma2 (PPARG2) is a nuclear hormone receptor of ligand-dependent transcription 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.

Item Type:Article
Refereed:Yes
Divisions:Interdisciplinary centres and themes > Institute for Cardiovascular and Metabolic Research (ICMR)
Faculty of Life Sciences > School of Chemistry, Food and Pharmacy > Department of Food and Nutritional Sciences > Human Nutrition Research Group
ID Code:34664
Publisher:Elsevier

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