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

Diabetes. 2010 Aug;59(8):2068-74. doi: 10.2337/db09-1386. Epub 2010 Apr 27.

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 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.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • 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
  • Ethnic Groups / genetics
  • European Continental Ancestry Group / genetics
  • Female
  • Genetic Variation*
  • Genome-Wide Association Study / methods
  • Genotype
  • Homeodomain Proteins / genetics*
  • Humans
  • India / epidemiology
  • Male
  • Middle Aged
  • PPAR gamma / genetics*
  • Potassium Channels, Inwardly Rectifying / genetics*
  • RNA-Binding Proteins / genetics*
  • Reference Values
  • TCF Transcription Factors / genetics*
  • Transcription Factor 7-Like 2 Protein
  • Transcription Factors / genetics*
  • Zinc Transporter 8
  • tRNA Methyltransferases

Substances

  • Cation Transport Proteins
  • Cyclin-Dependent Kinase Inhibitor p16
  • HHEX protein, human
  • Homeodomain Proteins
  • IGF2BP2 protein, human
  • Kir6.2 channel
  • PPAR gamma
  • Potassium Channels, Inwardly Rectifying
  • RNA-Binding Proteins
  • SLC30A8 protein, human
  • TCF Transcription Factors
  • TCF7L2 protein, human
  • Transcription Factor 7-Like 2 Protein
  • Transcription Factors
  • Zinc Transporter 8
  • tRNA Methyltransferases
  • Cyclin-Dependent Kinase 5
  • CDKAL1 protein, human