Pathophysiologic Mechanisms of Insulin Secretion and Signaling-Related Genes in Etiology of Polycystic Ovary Syndrome.

Zahra Shaaban,Mohammad Reza Jafarzadeh Shirazi,Fariborz Nowzari,Amir Amiri-Yekta,Arezoo Khoradmehr,Amin Tamadon,Hafiz Ishfaq Ahmad

doi:10.1155/2021/7781823

Zahra Shaaban, Mohammad Reza Jafarzadeh Shirazi + Show 5 more

Open Access

https://doi.org/10.1155/2021/7781823

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Abstract

Polycystic ovary syndrome (PCOS) is a common endocrinopathy in women. PCOS is characterized by anovulation, hyperandrogenism, polycystic ovaries, insulin resistance, and obesity. Despite the finding that the genetic origin of PCOS is well demonstrated in previous twin and familial clustering studies, genes and factors that can exactly explain the PCOS pathophysiology are not known. Objective(s). In this review, we attempted to identify genes related to secretion and signaling of insulin aspects of PCOS and their physiological functions in order to explain the pathways that are regulated by these genes which can be a prominent function in PCOS predisposition. Materials and Methods. For this purpose, published articles and reviews dealing with genetic evaluation of PCOS in women from peer-reviewed journals in PubMed and Google Scholar databases were included in this review. Results. The genomic investigations in women of different populations identified many candidate genes and loci that are associated with PCOS. The most important of them are INSR, IRS1-2, MTNR1A, MTNR1B, THADA, PPAR-γ2, ADIPOQ, and CAPN10. These are mainly associated with metabolic aspects of PCOS. Conclusions. In this review, we proposed that each of these genes may interrupt specific physiological pathways by affecting them and contribute to PCOS initiation. It is clear that the role of genes involved in insulin secretion and signaling is more critical than other pathways.

Highlights

Polycystic ovary syndrome (PCOS) is a common endocrinopathy in women
Results. e genomic investigations in women of different populations identified many candidate genes and loci that are associated with PCOS. e most important of them are insulin receptor (INSR), IRS1-2, melatonin receptor 1A (MTNR1A), MTNR1B, thyroid adenoma-associated (THADA), PPAR-c2, ADIPOQ, and calpain 10 (CAPN10). ese are mainly associated with metabolic aspects of PCOS
Insulin resistance and hyperinsulinemia in adolescents are seen in the early stages of PCOS [14], and adolescents girls with PCOS are exposed to the increased risk of impaired glucose tolerance and diabetes mellitus type 2 [15]

Summary

Introduction

Polycystic ovary syndrome (PCOS) is a common endocrinopathy in women. PCOS is characterized by anovulation, hyperandrogenism, polycystic ovaries, insulin resistance, and obesity. Due to the heterogeneity of PCOS, the exact pathophysiological pathway that initiates the syndrome has not been known yet Metabolic disorders such as insulin resistance, glucose intolerance, and type 2 diabetes are observed in PCOS patients [3]. E strong roles of inheritance and genetic background in PCOS development were confirmed based on twin and familial clustering studies [9, 10]. Unlike the increasing documents proving the heritability of PCOS and the effects of developmental origins of insulin resistance on PCOS development, the exact pathophysiological pathways in etiology of PCOS are not clear [11]. E aim of the present review is brief description of susceptible genes contributed to PCOS development that are related to metabolic pathways such as insulin secretion and signaling GWAS as a new approach presented a way for unbiased identification of genes without considering the probable role of causative variants [11]. e aim of the present review is brief description of susceptible genes contributed to PCOS development that are related to metabolic pathways such as insulin secretion and signaling

Objectives

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Results

Conclusion