Human Molecular Genetics Advance Access originally published online on September 12, 2007
Human Molecular Genetics 2007 16(23):2960-2971; doi:10.1093/hmg/ddm256
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Common genetic variation in calpain-10 gene (CAPN10) and diabetes risk in a multi-ethnic cohort of American postmenopausal women
1 Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02215, USA, 2 Department of Epidemiology, University of California at Los Angeles (UCLA), School of Public Health, Los Angeles, CA 90095, USA, 3 Molecular and Integrative Physiological Science Program, Department of Environmental Health, Harvard School of Public Health, Boston, MA 02115, USA, 4 Department of Human Genetics and 5 Department of Medicine, David Geffen School of Medicine UCLA, Los Angeles, CA 90095, USA, 6 Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA and 7 Center for Primary Care and Prevention, Brown Medical School, Memorial Hospital of Rhode Island, Pawtucket, RI 02860, USA
* To whom correspondence should be addressed at: Department of Epidemiology, UCLA School of Public Health, PO Box 951772, 650 Charles E. Young Drive South, Los Angeles, CA 90095, USA. Tel: +1 3102065862; Fax: +1 3102066039; Email: siminliu{at}ucla.edu
Received July 30, 2007; Accepted September 3, 2007
Calpain-10 (CAPN10) protein may play a role in glucose metabolisms, pancreatic ß-cell insulin secretion and thermogenesis. Emerging evidence has implicated a role of CAPN10 genetic variants in the risk of type 2 diabetes mellitus (T2DM). Previous association studies, however, have focussed only on several variants initially reported and provided inconsistent results. We conducted a large nested case–control study to comprehensively investigate the associations between common variations in CAPN10 gene and T2DM risk among postmenopausal women aged 50–79 years from the Women's Health Initiative Observational Study. After comprehensive screening in 244 randomly chosen control samples (n = 61 for each of four ethnic groups), we selected a total of 12 tagging single nucleotide polymorphisms (tSNPs) spanning 91 kb in CAPN10 and genotyped them in 1543 diabetes cases and 2132 matched controls (including 968 cases and 968 controls for whites, 366 and 732 for blacks, 152 and 303 for Hispanics and 98 and 195 for Asian/Pacific Islanders). There were no significant associations between any individual tSNP and T2DM, within either the full study sample or any specific ethnic group. Nor was there any evidence of association between common CAPN10 haplotypes and diabetes risk (global tests for differences in risk were P = 0.31 for overall common haplotypes, P = 0.44 for haplotypes in block 1 and P = 0.37 for haplotypes in block 2). In conclusion, we did not observe any significant associations of the common SNPs or haplotypes across the CAPN10 gene with diabetes risk in our large and ethnically diverse cohort of postmenopausal women.
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