Genetic approaches to polycystic ovarian syndrome

Purpose of review This review clarifies the challenges facing investigators in the search for polycystic ovarian syndrome candidate genes. Recent findings Evidence for fibillin 3 has emerged as a polycystic ovarian syndrome candidate gene. The sex hormone binding gene also shows promise, as does evidence for fetal programming and X-chromosome inactivation. Summary As with many complex disorders, the heritability of polycystic ovarian syndrome has eluded investigators. Although familial aggregation studies have demonstrated clearly a genetic component to the syndrome, simple Mendelian models do not characterize its mode of inheritance. Instead, multiple loci and epigenetic modification may play a role in the phenotype. The candidate gene approach relies upon improved statistical and technological methods to analyze potential genes based on biologic plausibility. Pathways that affect steroidogenesis, insulin resistance, gonadotropin function, and obesity provide potential genes for investigation. Obstacles such as phenotypic variability, lack of a male phenotype, multiple attempts at analysis, and small sample sizes hamper these efforts. Nevertheless, great care must be taken to apply rigorous standards as we proceed with genetic studies. In addition to increasing our knowledge of common disorders, potential benefits include personalized medicine, with pharmacogenetics allowing therapies tailored to the individual.