Nature Genetics
26, 163 - 175 (2000)
doi:10.1038/79876
Genetic variation in the gene encoding calpain-10 is associated with type 2 diabetes mellitusYukio Horikawa1, 2, 11, Naohisa Oda3, 11, Nancy J. Cox3, 4, 11, Xiangquan Li1, 2, Marju Orho-Melander5, Manami Hara1, Yoshinori Hinokio1, 2, Tom H. Lindner3, Hirosato Mashima2, Peter E.H. Schwarz1, 2, Laura del Bosque-Plata1, 2, Yohko Horikawa2, Yukie Oda2, Issei Yoshiuchi2, Susan Colilla4, Kenneth S. Polonsky3, Shan Wei6, Patrick Concannon6, Naoko Iwasaki7, Jan Schulze8, Leslie J. Baier9, Clifton Bogardus9, Leif Groop5, Eric Boerwinkle10, Craig L. Hanis10
& Graeme I. Bell1, 2, 3, 41
Howard Hughes Medical Institute, The University of Chicago, Chicago, Illinois, USA. 2
Department of Biochemistry and Molecular Biology, The University of Chicago, Chicago, Illinois, USA. 3
Department of Medicine, The University of Chicago, Chicago, Illinois, USA. 4
Department of Human Genetics, The University of Chicago, Chicago, Illinois, USA. 5
Department of Endocrinology, Malmö University Hospital, University of Lund, Malmö, Sweden. 6
Molecular Genetics Program, Virginia Mason Research Center, and Department of Immunology, University of Washington, Seattle, Washington, USA. 7
Diabetes Center, Tokyo Women's Medical University, Tokyo, Japan. 8
Department of Internal Medicine III, University Clinic Carl Gustav Carus of the Technical University, Dresden, Germany. 9
Department of Phoenix Epidemiology and Clinical Research Branch, National Institutes of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, Arizona, USA. 10
Human Genetics Center, The University of Texas Health Science Center at Houston, Houston, Texas, USA. 11
These authors contributed equally to this work.
Correspondence should be addressed to Graeme I. Bell g-bell@uchicago.eduType 2 or non-insulin-dependent diabetes mellitus (NIDDM) is the most common form of diabetes worldwide, affecting approximately 4% of the world's adult population. It is multifactorial in origin with both genetic and environmental factors contributing to its development. A genome-wide screen for type 2 diabetes genes carried out in Mexican Americans localized a susceptibility gene, designated NIDDM1, to chromosome 2. Here we describe the positional cloning of a gene located in the NIDDM1 region that shows association with type 2 diabetes in Mexican Americans and a Northern European population from the Botnia region of Finland. This putative diabetes-susceptibility gene encodes a ubiquitously expressed member of the calpain-like cysteine protease family, calpain-10 (CAPN10). This finding suggests a novel pathway that may contribute to the development of type 2 diabetes.
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