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

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.