title: Variation within the type 2 diabetes susceptibility gene calpain-10 and polycystic ovary syndrome.
abstract: Variation within the calpain-10 gene (CAPN10) has been proposed to account for linkage to type 2 diabetes on chromosome 2q in Mexican-Americans, and associations with diabetes have been reported in several other populations. Given the epidemiological, physiological, and genetic overlap between type 2 diabetes and polycystic ovary syndrome (PCOS), CAPN10 represents a strong candidate gene for a role in PCOS susceptibility. Using both family based and case-control association resources (146 parent-offspring trios; 185 additional PCOS cases; 525 control subjects, all of European ancestry), we sought association between CAPN10 variation and PCOS, focusing on four single nucleotide polymorphism (SNP) variants (SNP-44, SNP-43; SNP-19; SNP-63). On single-locus transmission disequilibrium analysis in the 146 trios, there was nominal evidence (P = 0.03) of excess transmission of the more common allele at SNP-63. This association was not, however, replicated in the case-control analysis. No other significant associations were observed at the single-locus or haplotype level in either the transmission-disequilibrium or case-control analyses. The relative risk for the high-risk diabetes susceptibility 112/121 genotype (SNPs 43-19-63) was 0.84 (95% confidence intervals, 0.40-1.71). No associations were seen with intermediate traits of relevance to diabetes and PCOS pathogenesis. We have found no evidence from these analyses that CAPN10 gene variation influences susceptibility to PCOS.
authors.affiliation: Complex Traits Analysis Group, Department of Medicine, Imperial College Genetics and Genomics Research Institute, Imperial College School of Medicine, London W12 0NN, UK.
authors.forename: Lema
authors.initials: L
authors.lastname: Haddad
authors.forename: Julie C
authors.initials: JC
authors.lastname: Evans
authors.forename: Neda
authors.initials: N
authors.lastname: Gharani
authors.forename: Carole
authors.initials: C
authors.lastname: Robertson
authors.forename: Karen
authors.initials: K
authors.lastname: Rush
authors.forename: Steven
authors.initials: S
authors.lastname: Wiltshire
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Frayling
authors.forename: Terence J
authors.initials: TJ
authors.lastname: Wilkin
authors.forename: Andrew
authors.initials: A
authors.lastname: Demaine
authors.forename: Ann
authors.initials: A
authors.lastname: Millward
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Hattersley
authors.forename: Gerry
authors.initials: G
authors.lastname: Conway
authors.forename: Nancy J
authors.initials: NJ
authors.lastname: Cox
authors.forename: Graeme I
authors.initials: GI
authors.lastname: Bell
authors.forename: Steve
authors.initials: S
authors.lastname: Franks
authors.forename: Mark I
authors.initials: MI
authors.lastname: McCarthy
mesh_terms: D000328:Adult; D002154:Calpain / Q000235:genetics*; D016022:Case-Control Studies; D002874:Chromosome Mapping; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D014644:Genetic Variation; D006801:Humans; D011085:Polycystic Ovary Syndrome / Q000235:genetics*; D019655:Quantitative Trait, Heritable
chemical_list: D002154:Calpain; C415197:calpain 10