Genetic variants in the calpain-10 gene and the development of type 2 diabetes in the Japanese population.
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.
Iwasaki
Naoko
N
Diabetes Center, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan. niwasaki@dmc.twmu.ac.jp.
Horikawa
Yukio
Y
Laboratory of Molecular Genetics, Department of Cell Biology, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi, Japan.
Tsuchiya
Takafumi
T
Departments of Biochemistry and Molecular Biology, Human Genetics and Medicine, The University of Chicago, Chicago, Illinois, USA.
Kitamura
Yutaka
Y
Department of Statistical Genetics, Institute of Rheumatology, Tokyo Women's Medical University, Tokyo, Japan.
Nakamura
Takahiro
T
Department of Statistical Genetics, Institute of Rheumatology, Tokyo Women's Medical University, Tokyo, Japan.
Tanizawa
Yukio
Y
Division of Molecular Analysis of Human Disorders, Department of Bio-Signal Analysis, Yamaguchi University Graduate School of Medicine, Ube, Japan.
Oka
Yoshitomo
Y
Division of Molecular Metabolism and Diabetes, Department of Internal Medicine, Tohoku University, Sendai, Japan.
Hara
Kazuo
K
Department of Metabolic diseases, Graduate School of Medicine and Faculty of Medicine, University of Tokyo, Tokyo, Japan.
Kadowaki
Takashi
T
Department of Metabolic diseases, Graduate School of Medicine and Faculty of Medicine, University of Tokyo, Tokyo, Japan.
Awata
Takuya
T
Division of Endocrinology and Diabetes, Department of Medicine, Saitama Medical School, Saitama, Japan.
Honda
Masashi
M
Shiseikai Daini Hospital, Tokyo, Japan.
Yamashita
Katsuko
K
Seijin Igaku Medical Clinic, Tokyo, Japan.
Oda
Naohisa
N
Department of Internal Medicine, Fujita Health University School of Medicine, Aichi, Japan.
Yu
Li
L
Laboratory of Molecular Genetics, Department of Cell Biology, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi, Japan.
Yamada
Norihiro
N
Laboratory of Molecular Genetics, Department of Cell Biology, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi, Japan.
Ogata
Makiko
M
Diabetes Center, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan.
Kamatani
Naoyuki
N
Department of Statistical Genetics, Institute of Rheumatology, Tokyo Women's Medical University, Tokyo, Japan.
Iwamoto
Yasuhiko
Y
Diabetes Center, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan.
Del Bosque-Plata
Laura
L
Departments of Biochemistry and Molecular Biology, Human Genetics and Medicine, The University of Chicago, Chicago, Illinois, USA.
Hayes
M Geoffrey
MG
Departments of Biochemistry and Molecular Biology, Human Genetics and Medicine, The University of Chicago, Chicago, Illinois, USA.
Cox
Nancy J
NJ
Departments of Biochemistry and Molecular Biology, Human Genetics and Medicine, The University of Chicago, Chicago, Illinois, USA.
Bell
Graeme I
GI
Departments of Biochemistry and Molecular Biology, Human Genetics and Medicine, The University of Chicago, Chicago, Illinois, USA.
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
D002154:Calpain; C415197:calpain 10