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Vollmert, C. ; Hahn, S.* ; Lamina, C. ; Huth, C. ; Kolz, M. ; Schöpfer-Wendels, A. ; Mann, K.* ; Bongardt, F* ; Mueller, J.C.* ; Kronenberg, F. ; Wichmann, H.-E. ; Herder, C.* ; Holle, R. ; Löwel, H. ; Illig, T. ; Janssen, O.E* ; KORA Study Group (Wichmann, H.-E. ; Holle, R. ; John, J. ; Illig, T. ; Meisinger, C.)

Calpain-10 variants and haplotypes are associated with polycystic ovary syndrome in Caucasians.

Am. J. Physiol. Endocrinol. Metab. 292, E836-E844 (2007)

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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.

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