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

Abstract

Aims/hypothesisEvaluation of the association of 31 common single nucleotide polymorphisms (SNPs) with fasting glucose, fasting insulin, HOMA-beta cell function (HOMA-β), HOMA-insulin resistance (HOMA-IR) and type 2 diabetes in the Indian population.MethodsWe 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.ResultsThe 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 β 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 β 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 β 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 (β = −0.05; p = 0.01) and CDKN2A/B (β = −0.05; p = 0.03) with HOMA-β. THADA variant (rs7578597) was associated with type 2 diabetes (OR 1.5; 95% CI 1.04, 2.22; p = 0.03).Conclusions/interpretationWe 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.Electronic supplementary materialThe online version of this article (doi:10.1007/s00125-011-2355-6) contains peer-reviewed but unedited supplementary material, which is available to authorised users.

Association of Common Genetic Variants with Diabetes and Metabolic Syndrome Related Traits in the Arizona Insulin Resistance Registry: A Focus on Mexican American Families in the Southwest

“…This is further supported by the fact that numerous associations between SNP rs7578597 in THADA and type 2 diabetes related traits have been observed in other populations [54, 55]. In our Mexican American population, we observed a nominal association with prediabetes, reaffirming the previous findings in other studies.…”

CD36Gene Variants and Their Association with Type 2 Diabetes in an Indian Population

“…23 Another study has shown association of 31 common polymorphisms with T2DM in Indian sib pairs. 24 The association between CD36 gene overexpression and presence of atherosclerotic risk factors, particularly diabetes, shown in this study is in agreement with a common etiology of the disease. 25 The role of the CD36 protein in lipid metabolism and metabolic syndrome prompted us to investigate the association of CD36 gene variants with T2DM.…”

Genetic Analysis of Atherosclerosis and Glucose Homeostasis in an Intercross Between C57BL/6 and BALB/cJ Apolipoprotein E–Deficient Mice

“…Cxcr4, Pask, Cntnap5a, Lct, and Pik3c2b are positional candidate genes for Bglu12 . Variants of these genes have been found to be associated with susceptibility to T2DM, fasting glucose, or insulin resistance in humans 62, 63,64, 65, 66, 67 .…”