Genetic Susceptibility to Joint Occurrence of Polycystic Ovary Syndrome and Hashimoto's Thyroiditis: How Far Is Our Understanding?

Abstract

Polycystic ovary syndrome (PCOS) and Hashimoto's thyroiditis (HT) are endocrine disorders that commonly occur among young women. A higher prevalence of HT in women with PCOS, relative to healthy individuals, is observed consistently. Combined occurrence of both diseases is associated with a higher risk of severe metabolic and reproductive complications. Genetic factors strongly impact the pathogenesis of both PCOS and HT and several susceptibility loci associated with a higher risk of both disorders have been identified. Furthermore, some candidate gene polymorphisms are thought to be functionally relevant; however, few genetic variants are proposed to be causally associated with the incidence of both disorders together.

Keywords: Hashimoto’s thyroiditis; association studies; autoimmune thyroid disease; genetic variants; polycystic ovary syndrome; susceptibility loci.

Figure 1

Schematic presentation of possible cross-linkages between PCOS and HT. Involvement of the most important genetic factors and molecular pathways. Treg cell dysregulation emerges as a critical point in the genetic and functional network linking the two diseases. In PCOS, genetic variation emphasizes the contribution of both hormonal imbalance (gonadotropins, androgens, and female sex hormones) and metabolic factors (IR and INS secretion), often interacting through a feedback loop. Suppression of TGF-β signaling pathway in combination with IR may lead to dysregulation of Treg cells and promotion of autoimmunity in women with PCOS (red line connections). Possible interaction of ncRNA (miRNA, lncRNA) with TGF-β signaling. The most important genes are indicated in blue; darker blue designates susceptibility genes for both diseases.