Abstract
Variation in the gene encoding the cysteine protease calpain-10 has been linked and associated with risk of type 2 diabetes. We have examined the effect of three polymorphisms in the calpain-10 gene (SNP-43, Indel-19, and SNP-63) on the development of type 2 diabetes in the Japanese population in a pooled analysis of 927 patients and 929 controls. We observed that SNP-43, Indel-19, and SNP-63 either individually or as a haplotype were not associated with altered risk of type 2 diabetes with the exception of the rare 111/221 haplogenotype (odds ratio (OR) =3.53, P=0.02). However, stratification based on the median age-at-diagnosis in the pooled study population (<50 and ≥50 years) revealed that allele 2 of Indel-19 and the 121 haplotype were associated with reduced risk in patients with later age-at-diagnosis (age-at-diagnosis ≥50 years OR=0.82 and 0.80, respectively; P=0.04 and 0.02). Thus, variation in the calpain-10 gene may affect risk of type 2 diabetes in Japanese, especially in older individuals.
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Acknowledgements
The authors thank Ms. A. Nogami, Ms. M. Y. Sagisaka, and Mr. M. Ikeda for their skillful technical assistance. This study was supported by Grants-in-Aid for Scientific Research C (10671084, 10470234) and for Scientific Research on Priority Areas Medical Genome Science from the Japan Ministry of Science, Education, Sports, Culture and Technology (12204102, 13204082, 14013059, 15012250), Novo Nordisk Foundation, the Naito Foundation (to N.I.) and Grants-in-Aid for Scientific Research B (13470223, 13557091) (to Y.H.), and U.S. Public Health Service (Grants DK-20595, −47486 and −55889). G.I.B. is an Investigator of the Howard Hughes Medical Institute.
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Naoko Iwasaki, Yukio Horikawa and Takafumi Tsuchiya contributed equally to this work.
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Iwasaki, N., Horikawa, Y., Tsuchiya, T. et al. Genetic variants in the calpain-10 gene and the development of type 2 diabetes in the Japanese population. J Hum Genet 50, 92–98 (2005). https://doi.org/10.1007/s10038-004-0225-5
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DOI: https://doi.org/10.1007/s10038-004-0225-5
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