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

The First Department of Medicine (Y.F., T.Sh., H.F., S.M., A.D., M.N., H.S., K.N.), Department of Metabolism and Clinical Nutrition (A.K., M.N.), and Department of Clinical Laboratory Medicine (T.Sa.), Wakayama Medical University, Wakayama 641-8509, Japan

Address all correspondence and requests for reprints to: Hiroto Furuta, M.D., Ph.D., The First Department of Medicine, Wakayama Medical University, 811-1 Kimiidera, Wakayama 641-8509, Japan. E-mail: hfuruta{at}wakayama-med.ac.jp.

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.

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				Y. Horikawa, K. Miyake, K. Yasuda, M. Enya, Y. Hirota, K. Yamagata, Y. Hinokio, Y. Oka, N. Iwasaki, Y. Iwamoto, et al. Replication of Genome-Wide Association Studies of Type 2 Diabetes Susceptibility in Japan J. Clin. Endocrinol. Metab., August 1, 2008; 93(8): 3136 - 3141. [Abstract] [Full Text] [PDF]