title: Calpain-10 variants and haplotypes are associated with polycystic ovary syndrome in Caucasians.
abstract: 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.
authors.affiliation: Institute of Epidemiology, GSF-National Research Center for Environment and Health, Institute of Epidemiology, Ingolstädter Landstrasse 1, D-85764 Neuherberg, Germany. vollmert@gsf.de
authors.forename: Caren
authors.initials: C
authors.lastname: Vollmert
authors.forename: Susanne
authors.initials: S
authors.lastname: Hahn
authors.forename: Claudia
authors.initials: C
authors.lastname: Lamina
authors.forename: Cornelia
authors.initials: C
authors.lastname: Huth
authors.forename: Melanie
authors.initials: M
authors.lastname: Kolz
authors.forename: Andreas
authors.initials: A
authors.lastname: Schöpfer-Wendels
authors.forename: Klaus
authors.initials: K
authors.lastname: Mann
authors.forename: Friedhelm
authors.initials: F
authors.lastname: Bongardt
authors.forename: Jakob C
authors.initials: JC
authors.lastname: Mueller
authors.forename: Florian
authors.initials: F
authors.lastname: Kronenberg
authors.forename: H-Erich
authors.initials: HE
authors.lastname: Wichmann
authors.forename: Christian
authors.initials: C
authors.lastname: Herder
authors.forename: Rolf
authors.initials: R
authors.lastname: Holle
authors.forename: Hannelore
authors.initials: H
authors.lastname: Löwel
authors.forename: Thomas
authors.initials: T
authors.lastname: Illig
authors.forename: Onno E
authors.initials: OE
authors.lastname: Janssen
mesh_terms: D000328:Adult; D002154:Calpain / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D011085:Polycystic Ovary Syndrome / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D044465:White People / Q000235:genetics*
chemical_list: D002154:Calpain; C415197:calpain 10