Genomic variants in polycystic ovary syndrome

Abstract

The polycystic ovary syndrome (PCOS) is a common disorder in premenopausal women, characterized by the presence, among other traits, of hyperandrogenism, insulin resistance, and hyperinsulinism. The familial aggregation of PCOS lead the interest to the molecular genetic basis of this syndrome, especially to the genes encoding proteins involved in androgen synthesis and the regulation of insulin synthesis and action. Considering the relationship between insulin resistance and chronic inflammation, and the clustering of inflammatory markers in PCOS patients, recent studies focused on the involvement of proinflammatory genotypes on the pathogenesis of PCOS. Mounting evidence suggest at present a complex model of inheritance for PCOS, in which predisposing and protecting genomic variants interact with environmental factors such as obesity and a sedentary lifestyle, finally leading to the classic phenotype of this syndrome. Moreover, the association of hyperandrogenism, insulin resistance and chronic inflammation raised the possibility of an increase risk of cardiovascular disease in women suffering from PCOS. In the present review we will summarize the most important findings published to date regarding the molecular genetic mechanisms underlying the association of PCOS with insulin resistance and chronic inflammation, and the possible interaction of these mechanisms with environmental factors.