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Peroxisome proliferator-activated receptor-\gamma co-activator-1\alpha(PGC-1\alpha) gene polymorphisms and their relationship to type 2 diabetes in Asian Indians

Vimaleswaran, KS and Radha, V and Ghosh, S and Majumder, PP and Deepa, R and Babu, HNS and Rao, MRS and Mohan, V (2005) Peroxisome proliferator-activated receptor-\gamma co-activator-1\alpha(PGC-1\alpha) gene polymorphisms and their relationship to type 2 diabetes in Asian Indians. In: Diabetic Medicine, 22 (11). pp. 1516-1521.

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Official URL: http://onlinelibrary.wiley.com/doi/10.1111/j.1464-...

Abstract

Aims The objective of the present investigation was to examine the relationship of three polymorphisms, Thr394Thr, Gly482Ser and +A2962G,of the peroxisome proliferator activated receptor-\gamma co-activator-1\alpha (PGC-1 alpha) gene with Type 2 diabetes in Asian Indians. Methods The study group comprised 515 Type 2 diabetic and 882 normal glucose tolerant subjects chosen from the Chennai Urban Rural Epidemiology Study, an ongoing population-based study in southern India. The three polymorphisms were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Haplotype frequencies were estimated using an expectation-maximization (EM)algorithm. Linkage disequilibrium was estimated from the estimates of haplotypic frequencies. Results The three polymorphisms studied were not in linkage disequilibrium. With respect to the Thr394Thr polymorphism, 20% of theType 2 diabetic patients (103/515) had the GA genotype compared with 12% of the normal glucose tolerance (NGT) subjects (108/882) (P =0.0004). The frequency of the A allele was also higher in Type 2 diabetic subjects (0.11) compared with NGT subjects (0.07) (P = 0.002).Regression analysis revealed the odds ratio for Type 2 diabetes for the susceptible genotype (XA) to be 1.683 (95% confidence intervals:1.264-2.241, P = 0.0004). Age adjusted glycated haemoglobin (P =0.003), serum cholesterol (P = 0.001) and low-density lipoprotein (LDL)cholesterol (P = 0.001) levels and systolic blood pressure (P = 0.001)were higher in the NGT subjects with the XA genotype compared with GG genotype. There were no differences in genotype or allelic distribution between the Type 2 diabetic and NGT subjects with respect to the Gly482Ser and +A2962G polymorphisms. Conclusions The A allele of Thr394Thr (G -> A) polymorphism of the PGC-1 gene is associated with Type 2 diabetes in Asian Indian subjects and the XA genotype confers 1.6 times higher risk for Type 2 diabetes compared with the GG genotype in this population.

Item Type: Journal Article
Additional Information: Copyright for this article belongs to Blackwell Publishing.
Department/Centre: Division of Biological Sciences > Biochemistry
Date Deposited: 23 Nov 2005
Last Modified: 18 Jul 2011 06:53
URI: http://eprints.iisc.ernet.in/id/eprint/4120

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