Endocrine Abstracts

Polycystic ovary syndrome (PCOS) represents the most common cause of anovulatory infertility and its etiology is still unknown. Gene expression profiles from human PCOS ovaries have identified dysregulated expression of genes encoding components of several biological pathways or systems such as Wnt signaling, extracellular matrix components, immunological factors and androgens which, seem to play a key role in the pathogenesis of PCOS.

Candidate genes have been extensively studied using Single Nucleotide Polymorphisms (SNP’s). The impact of functional SNP’s on Gonadotrophins, growth factors and their receptors as well as the consecutive enzymes of the steroid biosynthesis pathways have been assessed in PCOS. Up till now only two functional SNP’s have been consistently associated with PCOS. An FSH receptor and an aromatase polymorphism seem to be more prevalent in PCOS and are both associated discrete changes in the endocrine environment in PCOS.

Family studies and linkage analysis is hampered by the lack of large well phenotyped family cohorts. Recently we have studied PCOS patients from an isolated population aiming to map gene(s) involved in PCOS susceptibility. The genome wide association analysis revealed only weak evidence of association for some markers scattered over the genome. Taken these findings into account it seems that PCOS constitutes a complex genetic disease with multiple genetic contributors which, might in turn be modified through different environmental factors. The individual contribution of these genetic components to the phenotype of PCOS seems to be very limited and hence, detection of genetic factors is far from easy.