title: [Polymorphism in CYP11alpha and CYP17 genes and the etiology of hyperandrogenism in patients with polycystic ovary syndrome].
abstract: The polycystic ovary syndrome (PCOS) is a heterogeneous multifactorial endocrine metabolic disorder with genetic predisposition affecting 6% of women in the reproductive age. This syndrome is characterized by the presence of oligo-anovulation, hyperandrogenism and polycystic ovaries. Several genes have been postulated as responsible for the etiology of this disorder. Among these genes are those encoding the enzymes involved in the ovarian androgen biosynthesis. Two of the candidate genes are the CYP17 and the CYP11alpha, encoding the 17-alpha-hydroxylase (P45017alpha) and the cholesterol side chain cleavage (P450scc) respectively. The polymorphisms of these genes are linked to the development of an hyperandrogenic phenotype. The aim of this work was to analyze the allelic frequencies of such polymorphisms in a cohort of women with PCOS and to compare them with those of healthy women. Furthermore, the correlation between each allelic variant and the corresponding hyperandrogenic phenotype was also assessed. Therefore, 65 patients and 58 age matched healthy controls were analyzed. The serum levels of testosterone and the frequency of each polymorphism were determined. When the PCOS population was analyzed, a significant statistical difference was found when relating the group with the highest androgenemia level with the presence of A2/A2 genotype of CYP 17 gene, and a higher level of circulating androgen was found in PCO women carrying the 216- allele of CYP11alpha gene (that did not reach statistical significance). Our results suggest that both alleles play a minor role in the development of PCOS and could be a genetic risk marker of the hyperandrogenic phenotype.
authors.affiliation: Cátedra de Genética y Biología Molecular, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Argentina.
authors.forename: María S
authors.initials: MS
authors.lastname: Pérez
authors.forename: Gloria E
authors.initials: GE
authors.lastname: Cerrone
authors.forename: Haydée
authors.initials: H
authors.lastname: Benencia
authors.forename: Norma
authors.initials: N
authors.lastname: Márquez
authors.forename: Eduardo
authors.initials: E
authors.lastname: De Piano
authors.forename: Gustavo D
authors.initials: GD
authors.lastname: Frechtel
mesh_terms: D000728:Androgens / Q000032:analysis / Q000493:pharmacokinetics; D001682:Biological Availability; D016022:Case-Control Studies; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000235:genetics*; D005260:Female; D005819:Genetic Markers / Q000235:genetics; D006801:Humans; D017588:Hyperandrogenism / Q000235:genetics*; D011085:Polycystic Ovary Syndrome / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*; D012150:Polymorphism, Restriction Fragment Length; D013254:Steroid 17-alpha-Hydroxylase / Q000235:genetics*; D013739:Testosterone / Q000032:analysis / Q000493:pharmacokinetics
chemical_list: D000728:Androgens; D005819:Genetic Markers; D013739:Testosterone; D013254:Steroid 17-alpha-Hydroxylase; D002786:Cholesterol Side-Chain Cleavage Enzyme