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A novel association of a polymorphism in the first intron of adiponectin gene with type 2 diabetes, obesity and hypoadiponectinemia in Asian Indians

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Abstract

Adiponectin is an adipose tissue specific protein that is decreased in subjects with obesity and type 2 diabetes. The objective of the present study was to examine whether variants in the regulatory regions of the adiponectin gene contribute to type 2 diabetes in Asian Indians. The study comprised of 2,000 normal glucose tolerant (NGT) and 2,000 type 2 diabetic, unrelated subjects randomly selected from the Chennai Urban Rural Epidemiology Study (CURES), in southern India. Fasting serum adiponectin levels were measured by radioimmunoassay. We identified two proximal promoter SNPs (−11377C→G and −11282T→C), one intronic SNP (+10211T→G) and one exonic SNP (+45T→G) by SSCP and direct sequencing in a pilot study (n = 500). The +10211T→G SNP alone was genotyped using PCR-RFLP in 4,000 study subjects. Logistic regression analysis revealed that subjects with TG genotype of +10211T→G had significantly higher risk for diabetes compared to TT genotype [Odds ratio 1.28; 95% Confidence Interval (CI) 1.07–1.54; P = 0.008]. However, no association with diabetes was observed with GG genotype (P = 0.22). Stratification of the study subjects based on BMI showed that the odds ratio for obesity for the TG genotype was 1.53 (95%CI 1.3–1.8; P < 10−7) and that for GG genotype, 2.10 (95% CI 1.3–3.3; P = 0.002). Among NGT subjects, the mean serum adiponectin levels were significantly lower among the GG (P = 0.007) and TG (P = 0.001) genotypes compared to TT genotype. Among Asian Indians there is an association of +10211T→G polymorphism in the first intron of the adiponectin gene with type 2 diabetes, obesity and hypoadiponectinemia.

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Acknowledgments

The study was supported by a grant from the Department of Biotechnology (DBT) and Department of Science and Technology (DST), New Delhi, India. We also thank the Indian Council of Medical Research (ICMR). We thank the Chennai Wellingdon Corporate Foundation for their support for the CURES field studies. This is publication no 60 from CURES (CURES-60).

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Correspondence to Venkatesan Radha.

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Vimaleswaran, K.S., Radha, V., Ramya, K. et al. A novel association of a polymorphism in the first intron of adiponectin gene with type 2 diabetes, obesity and hypoadiponectinemia in Asian Indians . Hum Genet 123, 599–605 (2008). https://doi.org/10.1007/s00439-008-0506-8

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