title: Large-scale analysis of the relationship between CYP11A promoter variation, polycystic ovarian syndrome, and serum testosterone.
abstract: CYP11A, the gene encoding p450scc, a key enzyme in steroid biosynthesis, is a strong biological candidate for polycystic ovary syndrome (PCOS) susceptibility. Four of the five published studies that have examined CYP11A for evidence of linkage and/or association have reported significant relationships with polycystic ovary (PCO) status and/or serum testosterone levels. However, study sizes have been modest, and the current study aimed to reevaluate these findings using significantly larger clinical resources. A pair of CYP11A promoter microsatellites, including the pentanucleotide (D15S520) previously implicated in trait susceptibility, were genotyped in 371 PCOS patients of United Kingdom origin, using both case-control and family-based association methods, and in 1589 women from a population-based birth cohort from Finland characterized for PCO symptomatology and testosterone levels. Although nominally significant differences in allele and genotype frequencies at both loci were observed in the United Kingdom case-control study (for example, an excess of the pentanucleotide four-repeat allele in cases, P = 0.005), these findings were not substantiated in the other analyses, and no discernable relationship was seen between variation at these loci and serum testosterone levels. These studies indicate that the strength of, and indeed the existence of, associations between CYP11A promoter variation and androgen-related phenotypes has been substantially overestimated in previous studies.
authors.affiliation: Genomic Medicine, Faculty of Medicine, Reproductive and Developmental Biology, Imperial College, Hammersmith Campus, London W12 0NN, United Kingdom.
authors.forename: Michelle
authors.initials: M
authors.lastname: Gaasenbeek
authors.forename: Brenda L
authors.initials: BL
authors.lastname: Powell
authors.forename: Ulla
authors.initials: U
authors.lastname: Sovio
authors.forename: Lema
authors.initials: L
authors.lastname: Haddad
authors.forename: Neda
authors.initials: N
authors.lastname: Gharani
authors.forename: Amanda
authors.initials: A
authors.lastname: Bennett
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Groves
authors.forename: Karen
authors.initials: K
authors.lastname: Rush
authors.forename: Micaela J
authors.initials: MJ
authors.lastname: Goh
authors.forename: Gerard S
authors.initials: GS
authors.lastname: Conway
authors.forename: Aimo
authors.initials: A
authors.lastname: Ruokonen
authors.forename: Hannu
authors.initials: H
authors.lastname: Martikainen
authors.forename: Anneli
authors.initials: A
authors.lastname: Pouta
authors.forename: Saara
authors.initials: S
authors.lastname: Taponen
authors.forename: Anna-Liisa
authors.initials: AL
authors.lastname: Hartikainen
authors.forename: Stephanie
authors.initials: S
authors.lastname: Halford
authors.forename: Marjo-Riitta
authors.initials: MR
authors.lastname: Järvelin
authors.forename: Steve
authors.initials: S
authors.lastname: Franks
authors.forename: Mark I
authors.initials: MI
authors.lastname: McCarthy
mesh_terms: D000328:Adult; D000483:Alleles; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D018895:Microsatellite Repeats; D011085:Polycystic Ovary Syndrome / Q000097:blood* / Q000235:genetics*; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics*; D013739:Testosterone / Q000097:blood*
chemical_list: D013739:Testosterone; D002786:Cholesterol Side-Chain Cleavage Enzyme