Variation within the type 2 diabetes susceptibility gene calpain-10 and polycystic ovary syndrome.
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.
Haddad
Lema
L
Complex Traits Analysis Group, Department of Medicine, Imperial College Genetics and Genomics Research Institute, Imperial College School of Medicine, London W12 0NN, UK.
Evans
Julie C
JC
Gharani
Neda
N
Robertson
Carole
C
Rush
Karen
K
Wiltshire
Steven
S
Frayling
Timothy M
TM
Wilkin
Terence J
TJ
Demaine
Andrew
A
Millward
Ann
A
Hattersley
Andrew T
AT
Conway
Gerry
G
Cox
Nancy J
NJ
Bell
Graeme I
GI
Franks
Steve
S
McCarthy
Mark I
MI
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
D002154:Calpain; C415197:calpain 10