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

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.

The genetics of human obesity

“…For example, adiponectin, a hormone that plays a key role in regulation of glucose and fatty acids75 and has reduced levels in obesity and type 2 diabetes,76 has been found to be genetically associated with these diseases around the world 77–81. In addition, association studies of various nominated candidate genes have also implicated the genes encoding such factors as the cannabinoid receptor 1 ( CNR1 ), dopamine receptor 2 ( DRD2 ), serotonin receptor 2C ( HTR2C ), and SLC6A4, 82–86 but the most replicated of them is the Pro12Ala substitution in the peroxisome proliferator-activated receptor-gamma( PPARγ ) gene, which has been extensively associated with both obesity87 and type 2 diabetes 88.…”

Association of Adiponectin Polymorphism with Metabolic Syndrome Risk and Adiponectin Level with Stroke Risk: A Meta-Analysis

“…For example, individuals carrying ADIPOQ +45T>G polymorphism were found to be associated with type 2 diabetes mellitus in Chinese, however, conflicting results have been reported in Asian and European subjects5758. To our knowledge, this prospective study is the first to date to demonstrate the findings of studies about the association of ADIPOQ +45T>G with MS in the whole population together with a stratified analysis.…”

Principal-component-based multivariate regression for genetic association studies of metabolic syndrome components

“…SNP rs11926347, in an intron of ABCC5 (OMIM 60521), and SNP rs6795506, near the 5' end of AHSG (OMIM 138680), had extremely small p-values (Table 8). Among the other nine genes, ADIPOQ (OMIM 605441, 612556) has been widely reported to be associated with obesity and diabetes [21-24]; FNDC3B (OMIM 611909) is involved in positive regulation of adipogenesis [25]; and DGKG (OMIM 601854) and AHSG (OMIM 138680) have been reported to be associated with obesity-related metabolic traits [26,27]. The remaining genes have no reported relation to obesity-related metabolic traits based on our literature review.…”