Genetic abnormalities in polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) is a very common endocrinopathy and is the major cause of anovulatory infertility. It is also associated with an incr eased risk of non insulin dependent diabetes (NIDDM) in later life. Despite the importance of PCOS to women's health, little is known about its aetiol ogy. Because of the well known familial clustering of cases of PCOS, recent studies in our department have focused on clinical and molecular genetic s tudies in an attempt to identify key genes which may be involved in its aet iology. We have found evidence that a polymorphism in the regulatory region of CYP11a (encoding P450 cholesterol side chain cleavage, also an importan t enzyme in the steroidogenic pathway) is associated with and linked to PCO S. In examination of the insulin gene (INS), we have shown, in three separa te populations, that class III alleles in the INS-VNTR (the minisatellite i n the regulatory region of the insulin gene) are associated with PCOS. Vari ation in this element has also been implicated in the aetiology of NIDDM. W e propose that PCOS is an oligogenic disorder in which a small number of ke y genes interact with environmental factors (notably dietary), the balance of which factors determine the, typically heterogeneous, clinical and bioch emical phenotype.