A validation study of type 2 diabetes-related variants of the TCF7L2, HHEX, KCNJ11, and ADIPOQ genes in one endogamous ethnic group of north India

Ann Hum Genet. 2010 Jul;74(4):361-8. doi: 10.1111/j.1469-1809.2010.00580.x.

Abstract

The aim of this study was to validate the single nucleotide polymorphisms (SNPs) of four candidate genes (TCF7L2, HHEX, KCNJ11, and ADIPOQ) related to type 2 diabetes (T2D) in an endogamous population of north India; the Aggarwal population, having 18-clans. This endogamous population model was heavily supported by recent land mark work and we also verified the homogeneity of this population by clan-based stratification analysis. Two SNPs (rs4506565; rs7903146) in TCF7L2 were found to be significant (p-value = 0.00191; p-value = 0.00179, respectively), and odds ratios of 2.1 (dominant-model) and 2.0 (recessive-model) respectively, were obtained for this population. The TTT haplotype in the TCF7L2 gene was significantly associated with T2D. Waist-Hip ratio (WHR), systolic blood pressure (SBP), and age were significant covariates for increasing risk of T2D. Single-SNP, combined-SNPs and haplotype analysis provides clear evidence that the causal mutation is near to or within the significant haplotype (TTT) of the TCF7L2 gene. In spite of a culturally-learned sedentary lifestyle and fat-enriched dietary habits, WHR rather than body-mass-index emerged as a robust predictor of risk for T2D in this population.

Publication types

  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Adiponectin / genetics
  • Adult
  • Age Factors
  • Aged
  • Blood Glucose / genetics
  • Body Mass Index
  • Diabetes Mellitus, Type 2 / genetics*
  • Ethnicity / genetics
  • Female
  • Homeodomain Proteins / genetics*
  • Humans
  • India
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • Potassium Channels, Inwardly Rectifying / genetics*
  • Risk
  • TCF Transcription Factors / genetics*
  • Transcription Factor 7-Like 2 Protein
  • Transcription Factors / genetics*
  • Waist-Hip Ratio

Substances

  • ADIPOQ protein, human
  • Adiponectin
  • Blood Glucose
  • HHEX protein, human
  • Homeodomain Proteins
  • Kir6.2 channel
  • Potassium Channels, Inwardly Rectifying
  • TCF Transcription Factors
  • TCF7L2 protein, human
  • Transcription Factor 7-Like 2 Protein
  • Transcription Factors