Short Communication

Diabetologia

, Volume 50, Issue 4, pp 747-751

First online:

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

  • M. HorikoshiAffiliated withDepartment of Metabolic Diseases, Graduate School of Medicine, University of TokyoCREST, Japan Science and Technology Corporation (JST)
  • , K. HaraAffiliated withDepartment of Metabolic Diseases, Graduate School of Medicine, University of TokyoCREST, Japan Science and Technology Corporation (JST)
  • , C. ItoAffiliated withMedical Court Life Care Clinic
  • , R. NagaiAffiliated withDepartment of Cardiovascular Medicine, Graduate School of Medicine, University of Tokyo
  • , P. FroguelAffiliated withGenomics and Molecular Physiology of Metabolic Diseases, CNRS UMR
  • , T. KadowakiAffiliated withDepartment of Metabolic Diseases, Graduate School of Medicine, University of TokyoCREST, Japan Science and Technology Corporation (JST) Email author 

Abstract

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.

Keywords

Association Susceptibility gene Type 2 diabetes