Polycystic ovary syndrome (PCOS) is the most common endocrinopathy affecting women of childbearing age causing not only reproductive but also metabolic anomalies. PCOS women present with ovulatory dysfunction, abnormal hormones, hyperandrogenemia, obesity, and hyperinsulinemia. It is a heterogeneous disorder which results from interaction of multiple genes along with environmental factors. Insulin resistance is a central key element contributing to PCOS pathogenesis and is further aggravated by obesity. Insulin regulates metabolic homeostasis and contributes to ovarian steroidogenesis. Candidate gene analyses have dissected genes related to insulin secretion and action for their association with PCOS susceptibility. Although a large number of genomic variants have been shown to be associated with PCOS, no single candidate gene has emerged as a convincing biomarker thus far. This may be attributed to large amount of heterogeneity observed in this disorder. This review presents an overview of the polymorphisms in genes related to insulin signaling and their association with PCOS and its related traits. 1. Introduction Polycystic ovary syndrome (PCOS) is the major cause of anovulatory infertility affecting millions of women worldwide. Despite years of research and huge amounts of investment, the etiology of PCOS is still poorly understood [1]. It is typically characterized by chronic anovulation, excess androgen production, and presence of polycystic ovaries on ultrasound. Clinically these women present with irregular menses, hirsutism, acne and alopecia, and elevated LH？:？FSH ratio along with insulin and androgen excess. This syndrome also confers a greater risk of development of impaired glucose tolerance and subsequent type 2 diabetes mellitus (T2DM), as well as metabolic syndrome and cardiovascular diseases (CVD) in later life [2]. Insulin resistance, the hallmark feature of PCOS and its associated compensatory hyperinsulinemia, is seen in approximately 50–70% of affected women [3]. Central obesity is present in both lean and obese women with PCOS which further aggravates insulin resistance and worsens the aforementioned symptoms in these women [4]. 2. Insulin Resistance and PCOS Insulin which is a potent anabolic hormone controls diverse processes essential for tissue metabolism, growth, and survival. Binding of insulin to its receptor initiates a cascade of signaling events and activates an array of molecules by which insulin exerts its pleiotropic actions. The insulin receptor (INSR) is a membrane bound receptor with intrinsic tyrosine kinase
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