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Am J Physiol Endocrinol Metab 292: E836-E844, 2007. First published November 14, 2006; doi:10.1152/ajpendo.00584.2005
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Calpain-10 variants and haplotypes are associated with polycystic ovary syndrome in Caucasians

¹Institute of Epidemiology, Gesellschaft für Strahlen-Forschung (GSF)-National Research Center for Environment and Health, Neuherberg; ²Division of Endocrinology, Department of Medicine, University of Duisburg-Essen, Essen; ³Institute of Medical Informatics, Biometry and Epidemiology, Ludwig Maximilians University; ⁴Neurochemistry and Neurogenetics Laboratory, Department of Psychiatry and Psychotherapy and ⁵Institute of Medical Statistics and Epidemiology, Technical University, Munich, Germany; ⁶Division of Genetic Epidemiology, Department of Medical Genetics, Molecular, and Clinical Pharmacology, Innsbruck Medical University, Innsbruck, Austria; ⁷German Diabetes Clinic, German Diabetes Center, Leibniz Center at Heinrich Heine University, Düsseldorf; and ⁸Institute of Health Economics and Health Care Management, GSF-National Research Center of Environment and Health, Neuherberg, Germany

Submitted 25 November 2005 ; accepted in final form 10 November 2006

PCOS is known to be associated with an increased risk of T2DM and has been proposed to share a common genetic background with T2DM. Recent studies suggest that the Calpain-10 gene (CAPN10) is an interesting candidate gene for PCOS susceptibility. However, contradictory results were reported concerning the contribution of certain CAPN10 variants, especially of UCSNP-44, to genetic predisposition to T2DM, hirsutism, and PCOS. By means of MALDI-TOF MS technique, we genotyped an expanded single nucleotide polymorphism panel, including the CAPN10 UCSNP-44, -43, -56, ins/del-19, -110, -58, -63, and -22 in a sample of 146 German PCOS women and 606 population-based controls. Statistical analysis revealed an association between UCSNP-56 and susceptibility to PCOS with an odds ratio (OR) of 2.91 (95% CI = 1.51–5.61) for women carrying an AA genotype compared with GG. As expected, the 22-genotype of the ins/del-19 variant, which is in high linkage disequilibrium (r² = 0.98) with UCSNP-56, was also significantly associated (OR = 2.98, 95% CI = 1.55–5.73). None of the additionally tested variants alone showed any significant association with PCOS. A meta-analysis including our study (altogether 623 PCOS cases and 1,224 controls) also showed significant association only with ins/del-19. The most common haplotype TGG3AGCA was significantly associated with a lower risk for PCOS (OR = 0.487, P = 0.0057). In contrast, the TGA2AGCA haplotype was associated with an increased risk for PCOS (OR = 3.557, P = 0.0011). By investigating a broad panel of CAPN10 variants, our results pointed to an allele dose-dependent association of UCSNP-56 and ins/del-19 with PCOS.

single nucleotide polymorphism; genetic association study; metabolic syndrome; type 2 diabetes mellitus

Address for reprint requests: O. E. Janssen, Division of Endocrinology, Dept. of Medicine, University of Duisburg-Essen, Hufelandstrasse 55, D-45122 Essen, Germany (e-mail: onno.jannssen{at}uni-essen.de)