The role of polymorphism in various potential genes on polycystic ovary syndrome susceptibility and pathogenesis

Abstract

Polycystic ovary syndrome (PCOS) is the most common endocrinopathies affecting the early reproductive age in women, whose pathophysiology perplexes many researchers till today. This syndrome is classically categorized by hyperandrogenism and/or hyperandrogenemia, menstrual and ovulatory dysfunction, bulky multi follicular ovaries on Ultrasonography (USG), and metabolic abnormalities such as hyperinsulinemia, dyslipidemia, obesity. The etiopathogenesis of PCOS is not fully elucidated, but it seems that the hypothalamus-pituitary-ovarian axis, ovarian, and/or adrenal androgen secretion may contribute to developing the syndrome. Infertility and poor reproductive health in women’s lives are highly associated with elevated levels of androgens. Studies with ovarian theca cells taken from PCOS women have demonstrated increased androgen production due to augmented ovarian steroidogenesis attributed to mainly altered expression of critical enzymes (Cytochrome P450 enzymes: CYP17, CYP21, CYP19, CYP11A) in the steroid hormone biosynthesis pathway. Despite the heterogeneity of PCOS, candidate gene studies are the widely used technique to delineate the genetic variants and analyze for the correlation of androgen biosynthesis pathway and those affecting the secretion or action of insulin with PCOS etiology. Linkage and association studies have predicted the relationship between genetic variants and PCOS risk among families or populations. Several genes have been proposed as playing a role in the etiopathogenesis of PCOS, and the presence of mutations and/or polymorphisms has been discovered, which suggests that PCOS has a vital heritable component. The following review summarizes the influence of polymorphisms in crucial genes of the steroidogenesis pathway leading to intraovarian hyperandrogenism which can result in PCOS.

An update of polycystic ovary syndrome: causes and therapeutics options

“…Other candidate genes have recently been proposed in the literature, including FSHR (follicle-stimulating hormone receptor) [ 86 ], and AR androgen receptor [ 87 ]. Large prospective and randomized trials are needed: (i) to establish gene-based treatemnt guidelines; and (ii) to understand the interplay between different polymorphisms and other environmental/lifestyle factors [ 88 , 89 ].…”

A Review on CYP11A1, CYP17A1, and CYP19A1 Polymorphism Studies: Candidate Susceptibility Genes for Polycystic Ovary Syndrome (PCOS) and Infertility

“…Many studies have shown the impairment of androgen and ovulation pathways in women with PCOS, resulting in hyperandrogenism and ovulatory dysfunction. Among these biochemical pathways are genes associated with PCOS, including insulin secretion (e.g., INSR , IRS -1, INS ), chronic inflammation (e.g., TNF-α, IL-6), coagulation cascade and complement (e.g., VWF ), signalling (e.g., AMH , LHCGR , INS , ADIPOQ ), cancer (e.g., MMP , AR1 , INS ), and steroidogenesis (e.g., CYP11A1 , CYP17A1 , CYP19A1 ) pathways [ 33 , 34 ].…”

Metabolic and Molecular Mechanisms of Diet and Physical Exercise in the Management of Polycystic Ovarian Syndrome

“…Critical genes that encode for steroidogenic enzymes, including cytochrome P450 enzymes (CYP), have also been investigated. In this regard, polymorphisms in CYP11A, CYP17, CYP19 and CYP21 genes are related to the alteration in the steroidogenesis with an overproduction of androgen hormones [ 45 ]. Recent studies have demonstrated that CYP 17 5’-UTR MspA1 (rs743572) and CYP 19 (rs2414096) polymorphisms increase the susceptibility to develop PCOS in young women, altering different hormone genesis pathways [ 46 , 47 , 48 ].…”