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Genetic Variations in Calpain-10 Gene Are Not a Major Factor in the Occurrence of Type 2 Diabetes in Japanese

Laboratory of Molecular Genetics (Y.H., L.Y., J.T.), Department of Cell Biology, Institute for Molecular and Cellular Regulation, Gunma University, Gunma 371-8512; Department of Internal Medicine (N.O., S.I., K.F., M.M., M.I.), Fujita Health University School of Medicine, Aichi 470-1192; and Department of Metabolism and Clinical Nutrition (L.Y., Y.S.), Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan

Address all correspondence and requests for reprints to: Yukio Horikawa, M.D., Institute for Molecular and Cellular Regulation, Gunma University, 3-39-15 Showa-machi, Maebashi, Gunma 371-8512, Japan. E-mail: yhorikaw{at}showa.gunma-u.ac.jp.

The 112/121 haplotype combination defined by the UCSNP-43, -19, and -63 alleles in the calpain-10 gene is associated with type 2 diabetes in Mexican Americans. To determine whether this genetic variation constitutes risk of type 2 diabetes in Japanese, we investigated its frequency in 177 patients with type 2 diabetes and 172 controls. Though this variation occurs in Japanese more frequently than in Mexican Americans, there is no significant difference in frequency between diabetic (29.9%) and control (31.9%) subjects. We also screened all exons and the putative promoter of the calpain-10 gene for mutations in 96 of the genotyped patients, resulting in the identification of 7 coding variants, including 3 missense mutations and 5 nucleotide alterations in the promoter. However, their frequencies all are similar in patients and controls, suggesting that these genetic variations are not a major factor in the occurrence of type 2 diabetes in Japanese, although they could yet be associated with various phenotypes of the disease.

This study was supported by Grants-in-Aid for Creative Scientific Research, for Scientific Research A-C, and for Scientific Research on Priority Areas C from the Japanese Ministry of Science, Education, Sports, Culture and Technology, Comprehensive Research on Aging and Health, and Research on Human Genome, Tissue Engineering and Food Biotechnology from the Japanese Ministry of Health, Labor and Welfare, the Yamanouchi Foundation for Research on Metabolic Disorders, the Uehara Memorial Foundation, Suzuken Memorial Foundation, and the Japan Diabetes Foundation.

Abbreviations: BMI, Body mass index; CAPN10, calpain-10 gene; FFA, free fatty acid; HbA_1C, hemoglobin A_1C; OR, odds ratio; SNP, single-nucleotide polymorphism.

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