A genetic variation of the transcription factor 7-like 2 gene is associated with risk of type 2 diabetes in the Japanese population

Diabetologia. 2007 Apr;50(4):747-51. doi: 10.1007/s00125-006-0588-6. Epub 2007 Jan 24.


Aims/hypothesis: It has been suggested that transcription factor 7-like 2 protein (TCF7L2) plays an important role in glucose metabolism by regulating the production level of glucagon-like peptide-1, a hormone which modifies glucose-dependent insulin secretion. Recently, variants of TCF7L2 gene were reported to confer an increased risk of type 2 diabetes in three different samples from European and European-origin populations. We studied whether the single nucleotide polymorphisms (SNPs) in TCF7L2 were associated with type 2 diabetes in samples from a Japanese population.

Methods: Five SNPs were genotyped in three different sample sets. Association with type 2 diabetes was investigated in each, as well as in combined sample sets.

Results: The SNP rs7903146 was nominally associated with type 2 diabetes in the initial (p = 0.08) and two replication sample sets (p = 0.05 and 0.06). For the combined sample set, in which we successfully genotyped 1,174 type 2 diabetes patients and 823 control subjects, rs7903146 showed a significant association with type 2 diabetes (odds ratio = 1.69 [95% CI 1.21-2.36], p = 0.002) with the same direction as the previous reports in samples from European and European-origin populations. SNPs rs7903146 and rs7901695 were in complete linkage disequilibrium. The rest of the five SNPs (rs7895340, rs11196205 and rs12255372) did not show any significant associations with type 2 diabetes.

Conclusions/interpretation: The consistent association between rs7903146 in TCF7L2 and type 2 diabetes in different ethnic groups, including the Japanese population, suggests that TCF7L2 is a common susceptibility gene for type 2 diabetes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age of Onset
  • Aged
  • Alleles
  • Diabetes Mellitus, Type 2 / diagnosis*
  • Diabetes Mellitus, Type 2 / ethnology
  • Diabetes Mellitus, Type 2 / genetics*
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Genetic Variation*
  • Genotype
  • Humans
  • Insulin Resistance
  • Japan
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Risk
  • TCF Transcription Factors / genetics*
  • TCF Transcription Factors / physiology
  • Transcription Factor 7-Like 2 Protein


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