Journal Article

Impact of Common Variants of PPARG , KCNJ11 , TCF7L2 , SLC30A8 , HHEX , CDKN2A , IGF2BP2 , and CDKAL1 on the Risk of Type 2 Diabetes in 5,164 Indians

Tabassum, Rubina, Bhaskar, Seema, Dwivedi, Om Prakash, Prakash, Swami, Yajnik, Chittaranjan S., Kumar, M.V. Kranthi, Chavali, Sreenivas, Chandak, Giriraj R., Spurgeon, Charles J., Tandon, Nikhil, Ghosh, Saurabh, Chauhan, Ganesh, Mahajan, Anubha, Bharadwaj, Dwaipayan, Kulkarni, Smita R.

2010

Overview

Common variants in PPARG, KCNJ11, TCF7L2, SLC30A8, HHEX, CDKN2A, IGF2BP2, and CDKAL1 genes have been shown to be associated with type 2 diabetes in European populations by genome-wide association studies. We have studied the association of common variants in these eight genes with type 2 diabetes and related traits in Indians by combining the data from two independent case-control studies. We genotyped eight single nucleotide polymorphisms (PPARG-rs1801282, KCNJ11-rs5219, TCF7L2-rs7903146, SLC30A8-rs13266634, HHEX-rs1111875, CDKN2A-rs10811661, IGF2BP2-rs4402960, and CDKAL1-rs10946398) in 5,164 unrelated Indians of Indo-European ethnicity, including 2,486 type 2 diabetic patients and 2,678 ethnically matched control subjects. We confirmed the association of all eight loci with type 2 diabetes with odds ratio (OR) ranging from 1.18 to 1.89 (P = 1.6 x 10(-3) to 4.6 x 10(-34)). The strongest association with the highest effect size was observed for TCF7L2 (OR 1.89 [95% CI 1.71-2.09], P = 4.6 x 10(-34)). We also found significant association of PPARG and TCF7L2 with homeostasis model assessment of beta-cell function (P = 6.9 x 10(-8) and 3 x 10(-4), respectively), which looked consistent with recessive and under-dominant models, respectively. Our study replicates the association of well-established common variants with type 2 diabetes in Indians and shows larger effect size for most of them than those reported in Europeans.

• Publisher: American Diabetes Association
• Subject: Aged / Aged, 80 and over / Biological and medical sciences / Cation Transport Proteins - genetics / Cyclin-Dependent Kinase 5 - genetics / Cyclin-Dependent Kinase Inhibitor p16 - genetics / Diabetes Mellitus, Type 1 - epidemiology / Diabetes Mellitus, Type 1 - genetics / Diabetes Mellitus, Type 2 - genetics / Diabetes. Impaired glucose tolerance / Endocrine pancreas. Apud cells (diseases) / Endocrinopathies / Ethnic Groups - genetics / Etiopathogenesis. Screening. Investigations. Target tissue resistance / European Continental Ancestry Group - genetics / Female / Genetic aspects / Genetic Variation / Genetics / Genome-Wide Association Study - methods / Genotype / Homeodomain Proteins - genetics / Humans / India - epidemiology / Male / Medical sciences / Middle Aged / Potassium Channels, Inwardly Rectifying - genetics / PPAR gamma - genetics / Reference Values / Risk factors / RNA-Binding Proteins - genetics / Single nucleotide polymorphisms / TCF Transcription Factors - genetics / Transcription Factor 7-Like 2 Protein / Transcription Factors - genetics / tRNA Methyltransferases / Type 2 diabetes / Zinc Transporter 8