Association analysis of 31 common polymorphisms with type 2 diabetes and its related traits in Indian sib pairs

作者：Gupta V^*; Vinay D G; Rafiq S; Kranthikumar M V; Janipalli C S; Giambartolomei C; Evans D M; Mani K R; Sandeep M N; Taylor A E; Kinra S; Sullivan R M; Bowen L; Timpson N J; Smith G D; Dudbridge F; Prabhakaran D; Ben Shlomo Y; Reddy K S; Ebrahim S; Chandak G R

来源：Diabetologia, 2012, 55(2): 349-357.

DOI：10.1007/s00125-011-2355-6

• Association
• India
• Intermediate traits
• Polymorphisms
• Type 2 diabetes

Evaluation of the association of 31 common single nucleotide polymorphisms (SNPs) with fasting glucose, fasting insulin, HOMA-beta cell HOMA-beta), HOMA-insulin resistance (HOMA-IR) and type 2 diabetes in the Indian population. %26lt;br%26gt;We genotyped 3,089 sib pairs recruited in the Indian Migration Study from four cities in India (Lucknow, Nagpur, Hyderabad and Bangalore) for 31 SNPs in 24 genes previously associated with type 2 diabetes in European populations. We conducted within-sib-pair analysis for type 2 diabetes and its related quantitative traits. %26lt;br%26gt;The risk-allele frequencies of all the SNPs were comparable with those reported in western populations. We demonstrated significant associations of CXCR4 (rs932206), CDKAL1 (rs7756992) and TCF7L2 (rs7903146, rs12255372) with fasting glucose, with beta values of 0.007 (p = 0.05), 0.01 (p = 0.01), 0.007 (p = 0.05), 0.01 (p = 0.003) and 0.08 (p = 0.01), respectively. Variants in NOTCH2 (rs10923931), TCF-2 (also known as HNF1B) (rs757210), ADAM30 (rs2641348) and CDKN2A/B (rs10811661) significantly predicted fasting insulin, with beta values of -0.06 (p = 0.04), 0.05 (p = 0.05), -0.08 (p = 0.01) and -0.08 (p = 0.02), respectively. For HOMA-IR, we detected associations with TCF-2, ADAM30 and CDKN2A/B, with beta values of 0.05 (p = 0.04), -0.07 (p = 0.03) and -0.08 (p = 0.02), respectively. We also found significant associations of ADAM30 (beta = -0.05; p = 0.01) and CDKN2A/B (beta = -0.05; p = 0.03) with HOMA-beta. THADA variant (rs7578597) was associated with type 2 diabetes (OR 1.5; 95% CI 1.04, 2.22; p = 0.03). %26lt;br%26gt;We validated the association of seven established loci with intermediate traits related to type 2 diabetes in an Indian population using a design resistant to population stratification.

• 出版日期2012-2