Understanding polycystic ovarian syndrome pathogenesis: an updated of its genetic aspects

Polycystic ovary syndrome (PCOS) is the most frequent cause of female infertility. It is also characterized by metabolic defects that raise the risk for cardiovascular disease. Despite the progress in the definition of the clinical aspects of the syndrome, only very few definite data are available about the ethiopathogenetic mechanisms that subtend PCOS. It is likely that the PCOS phenotype derives from the interaction between environmental and genetic factors. While environmental factors have easily been investigated, the individuation of the genetic factors seem to be more complex. Indeed, PCOS appears to be inherited as a complex, polygenic trait. Several family studies have been conducted with the aim to clarify the genetic aspects of PCOS, but their findings are often conflicting and not conclusive.Moreover, it is difficult to establish with certainty which genes are involved and their effective role in the development of the syndrome because in PCOS, genetic analysis is hampered by low fecundity, lack of a male phenotype, absence of an animal model, and dissimilarity of the diagnostic criteria used to select the patients. Since multiple biochemical pathways are implicated in PCOS pathogenesis, genes of steroid hormone metabolism, gonadotropin release and action, insulin secretion and action, adipose tissue metabolism and others have been investigated. Nevertheless, none of them seems to play a key role in the ethiopathogenesis of PCOS. This article reviews the large body of literature generated to support the presence of genetic abnormalities in PCOS women by taking in consideration the most important studies regarding PCOS candidate genes.