Polymorphisms in the IDE-KIF11-HHEX Gene Locus Are Reproducibly Associated With Type 2 Diabetes in a Japanese Population

J Clin Endocrinol Metab. 2008 Jan;93(1):310-4. doi: 10.1210/jc.2007-1029. Epub 2007 Oct 30.

Abstract

Context: A genome-wide association study in the French population has detected that novel single-nucleotide polymorphisms (SNPs) in the IDE-KIF11-HHEX gene locus and the SLC30A8 gene locus are associated with susceptibility to type 2 diabetes.

Objective: We investigated whether SNPs in these loci were associated with type 2 diabetes in Japanese.

Design: Two SNPs, rs7923837 and rs1111875, in the IDE-KIF11-HHEX gene locus and one SNP, rs13266634, in the SLC30A8 gene locus were genotyped in Japanese type 2 diabetic patients (n = 405) and in nondiabetic control subjects (n = 340) using the TaqMan genotyping assay system.

Results: The G allele of rs7923837 was associated with type 2 diabetes [odds ratio 1.66, 95% confidence interval (CI) 1.28-2.15; P = 0.00014], following the same tendency as in the French population of the previous report. Heterozygous and homozygous carriers of the risk allele had odds ratios of 1.57 (95% CI 1.15-2.16; P = 0.0050) and 3.16 (95% CI 1.40-7.16; P = 0.0038) relative to noncarriers. Although the G allele was a major allele (66.5%) in the French population, it was a minor allele (23.8%) in Japanese. The G allele of rs1111875 was also associated with type 2 diabetes (odds ratio 1.42, 95% CI 1.13-1.78; P = 0.0024). Heterozygous and homozygous carriers of the risk allele had odds ratios of 1.31 (95% CI 0.97-1.77; P = 0.0810) and 2.40 (95% CI 1.34-4.32; P = 0.0028) relative to noncarriers. A significant association with type 2 diabetes was not observed for rs13266634.

Conclusions: Polymorphisms in the IDE-KIF11-HHEX gene locus are associated with susceptibility to type 2 diabetes across the boundary of race.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alleles
  • DNA / chemistry
  • DNA / genetics
  • Diabetes Mellitus, Type 2 / enzymology
  • Diabetes Mellitus, Type 2 / genetics*
  • Female
  • Genetic Predisposition to Disease
  • Genotype
  • Homeodomain Proteins / genetics*
  • Humans
  • Insulysin / genetics*
  • Japan
  • Kinesin / genetics*
  • Linear Models
  • Male
  • Middle Aged
  • Polymerase Chain Reaction
  • Polymorphism, Single Nucleotide
  • Transcription Factors / genetics*

Substances

  • HHEX protein, human
  • Homeodomain Proteins
  • KIF11 protein, human
  • Transcription Factors
  • DNA
  • Insulysin
  • Kinesin