Association of Common Variants of CDKN2A/2B Rs10811661 (C/T)and WFS1 Rs6446482 (C/G) to Type 2 Diabetes Mellitus in the Indian Population of Eastern Uttar Pradesh

Abstract

Aim: Recent genome-wide association studies (GWAS) have identified several unsuspected genes that significantly increase the risk of type 2 diabetes mellitus (T2DM). We aimed to replicate the association of a common variant each in CDKN2A/2B (rs10811661) and WFS1 (rs6446482) in the population of Eastern Uttar Pradesh, India. These variants have been identified to be differentially associated with T2DM in different ethnic groups in previous GWAS. Results: We found SNP rs10811661 of CDKN2A/2B (OR 1.50, 95% CI 1.109-2.032, P=0.009) and SNP rs6446482 of WFS1 (OR 1.43, 95% CI 1.074-1.896, P=0.014) as significant risk factors for T2DM in Eastern Uttar Pradesh population. Normal Glucose-Tolerant (NGT) subjects carrying risk allele of rs10811661 (C/T) and rs6446482 (C/G) polymorphisms had significantly higher Fasting Plasma Glucose (FPG) and 2-hour Postprandial Plasma Glucose (2h-PPPG) levels compared to non-carriers. Conclusion: Our study replicates the association of well established common variants of CDKN2A/2B rs10811661 (C/T) and WFS1 rs6446482 (C/G) with type 2 diabetes in the population of Eastern Uttar Pradesh, India. Interestingly, our data show larger effect size for both of the SNPs than those reported in European populations.