Refining the impact of TCF7L2 gene variants on type 2 diabetes and adaptive evolution

Nat Genet. 2007 Feb;39(2):218-25. doi: 10.1038/ng1960. Epub 2007 Jan 7.

Abstract

We recently described an association between risk of type 2diabetes and variants in the transcription factor 7-like 2 gene (TCF7L2; formerly TCF4), with a population attributable risk (PAR) of 17%-28% in three populations of European ancestry. Here, we refine the definition of the TCF7L2 type 2diabetes risk variant, HapB(T2D), to the ancestral T allele of a SNP, rs7903146, through replication in West African and Danish type 2 diabetes case-control studies and an expanded Icelandic study. We also identify another variant of the same gene, HapA, that shows evidence of positive selection in East Asian, European and West African populations. Notably, HapA shows a suggestive association with body mass index and altered concentrations of the hunger-satiety hormones ghrelin and leptin in males, indicating that the selective advantage of HapA may have been mediated through effects on energy metabolism.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • African Continental Ancestry Group
  • Asian Continental Ancestry Group
  • Biological Evolution*
  • Body Mass Index
  • Case-Control Studies
  • Diabetes Mellitus, Type 2 / genetics*
  • European Continental Ancestry Group
  • Female
  • Genetic Predisposition to Disease
  • Genetic Variation
  • Haplotypes
  • Humans
  • Iceland
  • Male
  • Polymorphism, Single Nucleotide*
  • Risk
  • Selection, Genetic
  • TCF Transcription Factors / genetics*
  • Transcription Factor 7-Like 2 Protein

Substances

  • TCF Transcription Factors
  • TCF7L2 protein, human
  • Transcription Factor 7-Like 2 Protein