title: Variants implicated in cortisone reductase deficiency do not contribute to susceptibility to common forms of polycystic ovary syndrome.
abstract: OBJECTIVE
  There are close phenotypic similarities between cortisone reductase deficiency (CRD), a rare abnormality of cortisone metabolism, and polycystic ovary syndrome (PCOS). As there is evidence that CRD results from digenic mutations involving the genes encoding 11beta-hydroxysteroid dehydrogenase type 1 (HSD11B1) and hexose-6-phosphate dehydrogenase (H6PD), we sought to establish whether CRD-associated variants in these genes, individually or in combination, influence susceptibility to PCOS.
  
  
  METHODS
  Case-control, family-based association and quantitative-trait analyses.
  
  
  METHODS
  A UK case sample comprising 256 nuclear families ascertained from a PCOS offspring and 213 singleton PCOS cases plus 549 control subjects.
  
  
  METHODS
  All subjects were genotyped for CRD-related variants in HSD11B1 (rs12086634) and H6PD (rs6688832). Testosterone was measured with an in-house radioimmunoassay using ether extraction and dextran-coated charcoal separation.
  
  
  RESULTS
  Case-control analyses revealed no differences in genotype distribution between PCOS and controls for rs12086634 or rs6688832 (both P = 0.84). Three per cent of cases and 2.4% of controls had genotype combinations (three or more variant alleles at the two sites) considered characteristic of CRD (P = 0.73). There were no departures from expectation in the family-based association studies, and no significant associations between genotypes (individually or in combination) and BMI, WHR or testosterone.
  
  
  CONCLUSIONS
  The variants in HSD11B1 and H6PD typed, though implicated in causation of CRD, do not influence susceptibility to PCOS. It seems likely that additional variants within these genes are required for the development of CRD.
authors.affiliation: Division of Medical Sciences, Institute of Biomedical Research, University of Birmingham, Birmingham, UK.
authors.forename: Nicole
authors.initials: N
authors.lastname: Draper
authors.forename: Brenda L
authors.initials: BL
authors.lastname: Powell
authors.forename: Steve
authors.initials: S
authors.lastname: Franks
authors.forename: Gerard S
authors.initials: GS
authors.lastname: Conway
authors.forename: Paul M
authors.initials: PM
authors.lastname: Stewart
authors.forename: Mark I
authors.initials: MI
authors.lastname: McCarthy
mesh_terms: D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000235:genetics*; D000328:Adult; D002237:Carbohydrate Dehydrogenases / Q000235:genetics*; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D003349:Cortisone Reductase / Q000172:deficiency / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D011085:Polycystic Ovary Syndrome / Q000201:enzymology* / Q000235:genetics*; D019655:Quantitative Trait, Heritable
chemical_list: D002237:Carbohydrate Dehydrogenases; C020552:galactose-6-phosphate dehydrogenase; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; D003349:Cortisone Reductase