Abstract 3227: Contribution Of Known Genetic Factors To Increased Risk Of Type-2 Diabetes In Indian Asians

Abstract

Background. Type-2 diabetes (T2D) is 2– 4 fold more common amongst Indian Asians than North American and European whites, and is a major contributor to two-fold higher cardiovascular disease mortality in Asians. We investigated whether genetic variation in the validated T2D genes, contributes to the increased risk of T2D amongst Indian Asians, compared to European whites. Methods. We examined the association of genetic variants in the 16 validated T2D genes with T2D amongst 9,776 Indian Asian and 4,407 European white men and women, aged 35–75 years, participating in the London Life Sciences Prospective Population (LOLIPOP) study. Genotyping was performed by competitive allele-specific PCR (KASPar). Results. Indian Asians had higher T2D prevalence (20.9% vs 8.7%, P<0.001), despite lower age (50.3±10.9 vs 52.1±11.6, P<0.001) and body mass index (26.9±4.1 vs 27.6±4.7, P<0.001), compared to Europeans. Genotyping confirmed association of WFS1, SLC30A8, PPARG, IGF2BP2, TCF7L2, JAZF1, CDKN2A/B, HHEX/IDE and FTO with T2D in both populations (P<0.05). Associations of CDKAL1 , KCNJ11, THADA, CDC123-CAMK1D, ADAMTS9, TSPAN8-LGR5 or NOTCH2 with T2D did not reach statistical significance. SNP risk allele frequency was higher for six, but lower for nine, in Indian Asians compared to Europeans. In regression analysis, risk of T2D remained 3.6 (95%CI 3.2– 4.1, P<0.001) fold higher amongst Indian Asians compared to Europeans, despite adjustment for age, body mass index and known genetic factors. Discussion. Known genetic variants show similar association with T2D, and have similar risk allele frequencies, amongst Indian Asians and Europeans. These genetic factors do not account for the three-fold increased risk of T2D amongst Indian Asians.