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

  1. Giriraj R. Chandak2
  1. 1Functional Genomics Unit, Institute of Genomics and Integrative Biology (CSIR), Delhi, India;
  2. 2Genome Research Group, Centre for Cellular and Molecular Biology (CSIR), Hyderabad, India;
  3. 3Diabetes Unit, King Edward Memorial Hospital and Research Centre, Rasta Peth, Pune, India;
  4. 4Human Genetics Unit, Indian Statistical Institute, Kolkata, India;
  5. 5Department of Endocrinology, All India Institute of Medical Sciences, New Delhi, India.
  1. Corresponding authors: Dwaipayan Bharadwaj, db{at}igib.res.in, and Giriraj R. Chandak, chandakgrc{at}ccmb.res.in.
  1. G.C. and C.J.S. contributed equally to this work.

Abstract

OBJECTIVE 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.

RESEARCH DESIGN AND METHODS 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.

RESULTS 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 × 10−3 to 4.6 × 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 × 10−34). We also found significant association of PPARG and TCF7L2 with homeostasis model assessment of β-cell function (P = 6.9 × 10−8 and 3 × 10−4, respectively), which looked consistent with recessive and under-dominant models, respectively.

CONCLUSIONS 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.

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  1. Diabetes vol. 59 no. 8 2068-2074
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