title: Genetic variants in the calpain-10 gene and the development of type 2 diabetes in the Japanese population.
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 > or =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 > or =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.
authors.affiliation: Diabetes Center, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan. niwasaki@dmc.twmu.ac.jp.
authors.forename: Naoko
authors.initials: N
authors.lastname: Iwasaki
authors.affiliation: Laboratory of Molecular Genetics, Department of Cell Biology, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi, Japan.
authors.forename: Yukio
authors.initials: Y
authors.lastname: Horikawa
authors.affiliation: Departments of Biochemistry and Molecular Biology, Human Genetics and Medicine, The University of Chicago, Chicago, Illinois, USA.
authors.forename: Takafumi
authors.initials: T
authors.lastname: Tsuchiya
authors.affiliation: Department of Statistical Genetics, Institute of Rheumatology, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Kitamura
authors.affiliation: Department of Statistical Genetics, Institute of Rheumatology, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Nakamura
authors.affiliation: Division of Molecular Analysis of Human Disorders, Department of Bio-Signal Analysis, Yamaguchi University Graduate School of Medicine, Ube, Japan.
authors.forename: Yukio
authors.initials: Y
authors.lastname: Tanizawa
authors.affiliation: Division of Molecular Metabolism and Diabetes, Department of Internal Medicine, Tohoku University, Sendai, Japan.
authors.forename: Yoshitomo
authors.initials: Y
authors.lastname: Oka
authors.affiliation: Department of Metabolic diseases, Graduate School of Medicine and Faculty of Medicine, University of Tokyo, Tokyo, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Hara
authors.affiliation: Department of Metabolic diseases, Graduate School of Medicine and Faculty of Medicine, University of Tokyo, Tokyo, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kadowaki
authors.affiliation: Division of Endocrinology and Diabetes, Department of Medicine, Saitama Medical School, Saitama, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Awata
authors.affiliation: Shiseikai Daini Hospital, Tokyo, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Honda
authors.affiliation: Seijin Igaku Medical Clinic, Tokyo, Japan.
authors.forename: Katsuko
authors.initials: K
authors.lastname: Yamashita
authors.affiliation: Department of Internal Medicine, Fujita Health University School of Medicine, Aichi, Japan.
authors.forename: Naohisa
authors.initials: N
authors.lastname: Oda
authors.affiliation: Laboratory of Molecular Genetics, Department of Cell Biology, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi, Japan.
authors.forename: Li
authors.initials: L
authors.lastname: Yu
authors.affiliation: Laboratory of Molecular Genetics, Department of Cell Biology, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi, Japan.
authors.forename: Norihiro
authors.initials: N
authors.lastname: Yamada
authors.affiliation: Diabetes Center, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan.
authors.forename: Makiko
authors.initials: M
authors.lastname: Ogata
authors.affiliation: Department of Statistical Genetics, Institute of Rheumatology, Tokyo Women's Medical University, Tokyo, Japan.
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Kamatani
authors.affiliation: Diabetes Center, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan.
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Iwamoto
authors.affiliation: Departments of Biochemistry and Molecular Biology, Human Genetics and Medicine, The University of Chicago, Chicago, Illinois, USA.
authors.forename: Laura
authors.initials: L
authors.lastname: Del Bosque-Plata
authors.affiliation: Departments of Biochemistry and Molecular Biology, Human Genetics and Medicine, The University of Chicago, Chicago, Illinois, USA.
authors.forename: M Geoffrey
authors.initials: MG
authors.lastname: Hayes
authors.affiliation: Departments of Biochemistry and Molecular Biology, Human Genetics and Medicine, The University of Chicago, Chicago, Illinois, USA.
authors.forename: Nancy J
authors.initials: NJ
authors.lastname: Cox
authors.affiliation: Departments of Biochemistry and Molecular Biology, Human Genetics and Medicine, The University of Chicago, Chicago, Illinois, USA.
authors.forename: Graeme I
authors.initials: GI
authors.lastname: Bell
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D002154:Calpain / Q000235:genetics*; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005260:Female; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012307:Risk Factors
chemical_list: D002154:Calpain; C415197:calpain 10