Fat mass and Obesity Associated (FTO) gene and polycystic ovary syndrome: Insight into pathogenesis and association with insulin resistance

Abstract

Polycystic ovary syndrome (PCOS) is a metabolic and endocrine disorder affecting the global population, originally named as “schlerocystic ovaries”, “multicystic ovaries”, “Stein Leventhal Syndrome”. Obesity is believed to play a central role in the development of PCOS, as women with this condition are reported to be overweight or obese and the effect of excess weight is inconsistent. Numerous hormonal imbalances, including hyperandrogenism, insulin resistance (IR), and hyperinsulinemia, are reported to be present. The hypothalamus-hypophysis-ovary axis appears to be disrupted by insulin, and insulin resistance in ovarian tissue leads to impaired metabolic signalling but intact mitogenic and steroidogenic activity, favouring hyperandrogenemia, is thought to be the primary cause of PCOS. The metabolic issues of PCOS seem to have IR as a common pathophysiologic mechanism, which is described as a metabolic state marked by a reduction in cellular responsiveness to insulin signalling. Despite the fact that IR plays a role in the development of PCOS, patients exhibit unique ovarian dysfunction-causing processes that are unrelated to IR. PCOS is a polygenic and multifactorial syndrome/disorder and many genes have been associated with PCOS such as fat mass and obesity-associated (FTO) gene. The review article presents the current understanding of the disease and the clinical spectrum and genetic variants associated with PCOS. The mechanisms by which variants in the genes confer risk of PCOS and the genetic elements underlying PCOS remain to be determined. Elucidation of genetic markers and cellular pathways underlying PCOS will be useful in understanding the pathophysiology of this syndrome.

Keywords

• FTO
• PCOS
• Obesity
• Gene polymorphism
• Metabolic syndrome