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1 Institute of Epidemiology, GSF-National Research Center for Environment and Health, Neuherberg, Germany
2 Division of Endocrinology, Department of Medicine, University of Duisburg-Essen, Essen, Germany
3 Institute of Epidemiology, GSF-National Research Center for Environment and Health, Neuherberg, Germany; Institute of Medical Informatics, Biometry and Epidemiology, Chair of Epidemiology, Ludwig Maximilians University, Munich, Germany
4 Neurochemistry and Neurogenetics Laboratory, Department of Psychiatry and Psychotherapy, Technical University Munich, Munich, Germany; Institute of Medical Statistics and Epidemiology, Technical University Munich, Munich, Germany
5 Institute of Epidemiology, GSF-National Research Center for Environment and Health, Neuherberg, Germany; Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Innsbruck Medical University, Innsbruck, Austria
6 German Diabetes Clinic, German Diabetes Center, Leibniz Center at Heinrich Heine University, Duesseldorf, Germany
7 Institute of Health Economics and Health Care Management, GSF-National Research Center for Environment and Health, Neuherberg, Germany
8 The KORA group consists of H.-E. Wichmann (speaker), H. Loewel, C. Meisinger, T. Illig, R. Holle, J. John, and their coworkers,, Germany
* To whom correspondence should be addressed. E-mail: vollmert{at}gsf.de.
Polycystic ovary syndrome (PCOS) is known to be associated with an increased risk of type 2 diabetes mellitus (T2DM) and has been proposed to share a common genetic background with T2DM. Recent studies suggest the Calpain 10 gene (CAPN10) being 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 SNP 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 to 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 further tested variants alone showed any significant association with PCOS. A meta-analysis including our study (altogether 623 PCOS cases and 1224 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). In conclusion, 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.
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  M.O. Goodarzi, J.F. Maher, J. Cui, X. Guo, K.D. Taylor, and R. Azziz FEM1A and FEM1B: novel candidate genes for polycystic ovary syndrome Hum. Reprod., August 29, 2008; (2008) den324v1. [Abstract] [Full Text] [PDF]
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