مقاله انگلیسی رایگان در مورد ژنتیک مرتبط با هیپرآندروژنیسم در پاتوفیزیولوژی PCOS – هینداوی 2018

Polycystic ovary syndrome affects scores of women worldwide with a prevalence of nearly 6–10% of premenopausal women [1]. Typical features of PCOS comprise distorted gonadotropin ratios, chronic anovulation, and subsequently irregular menstrual cycles, insulin resistance, increased androgen levels, and appearance of polycystic ovarian morphology upon ultrasound imaging [2]. Besides reproductive anomalies, these women are at an increased risk of developing type II diabetes, metabolic syndrome, and cardiovascular diseases (CVD), with subclinical markers being detected at earlier ages. While a clear-cut origin of PCOS has not emerged to explain its underlying pathophysiology, androgen excess and insulin resistance are reported to be the pivotal pathogenic drivers which extend reproductive, metabolic, and cosmetic consequences to affected women. The ovary remains the primary source of hyperandrogenism in women with PCOS which is mainly attributed to thecal cell hyperplasia leading to intense ovarian steroidogenesis. Evidence suggests that hyperandrogenism is an important factor in promoting anovulation due to follicular arrest [3] and high androgen level has been linked to reduced oocyte developmental competence and maturation rates. Further testosterone has been correlated with fertilization rates, embryo development, and miscarriage rates in women with PCOS [4]. Adrenal androgen excess has been reported in 20–30% of women with PCOS possibly due to defects in cortisol metabolism or common steroid pathway biosynthesis enzymes [5]. Apart from modifying reproductive outcomes, hyperandrogenemia also predicts severity of cardiometabolic profiles and CVD risk [6]. A recent meta-analysis has accentuated that hyperandrogenemia unfavourably influences the incidence of dyslipidemia, indices of insulin resistance, and metabolic syndrome risk [7]. The possibility of a genetic basis of hyperandrogenemia in PCOS has been recognized early [8] and candidate gene studies investigating the association of genes involved in androgen synthesis and action have strengthened this concept further [9, 10]. In the present review, we have outlined studies detailing the association of polymorphisms in these genes with PCOS susceptibility and its related traits.