Association of adiponectin (AdipoQ) and sulphonylurea receptor (ABCC8) gene polymorphisms with Type 2 Diabetes in North Indian population of Punjab

Abstract

In Type 2 Diabetes (T2D), adiponectin (AdipoQ) and sulphonylurea receptor genes (ABCC8) are important targets for candidate gene association studies. The single nucleotide polymorphisms (SNPs) in these genes have been associated with features of the metabolic syndrome across various populations. The present case-control study undertaken in the population of Punjab, evaluates the association of +45T>G polymorphism in AdipoQ gene; and Exon16-3C>T as well as Exon18C>T polymorphisms in ABCC8 gene with T2D. These SNPs were genotyped in 200 T2D cases and 200 non-diabetic healthy controls using the PCR-RFLP method. The frequency of the minor G-allele for AdipoQ+45(T>G) polymorphism was significantly higher in T2D cases (29.0%) than in controls (21.5%) [P=0.02, OR=1.49 (1.07-2.04)]. The genetic model analysis revealed that the G-allele cumulatively provides nearly 1.59-1.78 fold increased risk to T2D under the additive (P=0.009; OR=1.59, 1.12-2.25 at 95% CI), dominant (TG/GG vs. TT) (P=0.034, OR=1.64, 1.04-2.56 at 95% CI) and codominant model (TG vs. TT/GG) (P=0.014; OR=1.78, 1.12-2.82 at 95% CI) after adjusting for confounding factors. However, no difference in the distribution of genotype and allele frequencies was observed for both the ABCC8 polymorphisms. The distribution of obesity profiles (BMI, WC and WHR) was also significantly different between cases and controls (P<0.05). Higher BMI and central obesity were observed to increase the risk of T2D. G-allele of +45(T>G) polymorphism in the adiponectin gene appears to be associated with increased risk of T2D, but the polymorphisms in sulphonylurea receptor gene do not seem to be associated with T2D in the population of Punjab.

Keywords: ABCC8/SUR1; ADA; ANOVA; AdipoQ; Adiponectin; American Diabetic Association; Analysis of Variance; BMI; Body Mass Index; CAD; CI; Confidence Interval; Coronary Artery Disease; DBP; Diastolic Blood Pressure; EDTA; Ethylene diamine tetra acetic acid; HWE; Hardy-Weinberg Equilibrium; IDF; IR; Insulin Resistance; International Diabetes Federation; LD; Linkage Disequilibrium; OR; Odds Ratio; PCR-RFLP; Polymerase Chain Reaction-Restriction Fragment Length Polymorphism; SBP; SD; SNP; SPSS; Single Nucleotide Polymorphism; Standard Deviation; Statistical Package for the Social Sciences; Sulphonylurea receptor; Systolic Blood Pressure; T2D; TZD; Thiazolidinediones; Type 2 Diabetes; WC; WHR\; Waist Circumference; Waist Hip Ratio.