title: Genetic abnormalities in polycystic ovary syndrome.
abstract: Polycystic ovary syndrome (PCOS) is a very common endocrinopathy and is the major cause of anovulatory infertility. It is also associated with an increased risk of non insulin dependent diabetes (NIDDM) in later life. Despite the importance of PCOS to women's health, little is known about its aetiology. Because of the well-known familial clustering of cases of PCOS, recent studies in our department have focused on clinical and molecular genetic studies in an attempt to identify key genes which may be involved in its aetiology. We have found evidence that a polymorphism in the regulatory region of CYP11a (encoding P450 cholesterol side chain cleavage, also an important enzyme in the steroidogenic pathway) is associated with and linked to PCOS. In examination of the insulin gene (INS), we have shown, in three separate populations, that class III alleles in the INS-VNTR (the minisatellite in the regulatory region of the insulin gene) are associated with PCOS. Variation in this element has also been implicated in the aetiology of NIDDM. We propose that PCOS is an oligogenic disorder in which a small number of key genes interact with environmental factors (notably dietary), the balance of which factors determine, the typically heterogeneous, clinical and biochemical phenotype.
authors.affiliation: Department of Reproductive Science and Medicine, Imperial College School of Medicine, St Mary's Hospital, London, UK.
authors.forename: S
authors.initials: S
authors.lastname: Franks
authors.forename: N
authors.initials: N
authors.lastname: Gharani
authors.forename: M
authors.initials: M
authors.lastname: McCarthy
mesh_terms: D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics; D005260:Female; D006801:Humans; D007328:Insulin / Q000235:genetics; D018598:Minisatellite Repeats; D011085:Polycystic Ovary Syndrome / Q000235:genetics*; D013254:Steroid 17-alpha-Hydroxylase / Q000235:genetics
chemical_list: D007328:Insulin; D013254:Steroid 17-alpha-Hydroxylase; D002786:Cholesterol Side-Chain Cleavage Enzyme