PCOS-GWAS Susceptibility Variants in THADA, INSR, TOX3, and DENND1A Are Associated With Metabolic Syndrome or Insulin Resistance in Women With PCOS

Tian, Ye; Li, Jingyu; Su, Shizhen; Cao, Yongzhi; Zhao, Wei; Zhao, Shigang; Zhao, Han

doi:10.3389/fendo.2020.00274

Cited by 42 publications

(30 citation statements)

References 48 publications

(56 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, some PCOS candidate genes, such as thyroid adenoma associated ( THADA ) and insulin receptor ( INSR) , have been associated with metabolic syndrome and impaired glucose regulation in PCOS and type 2 diabetes [ 77 ], suggesting genetic contributions to metabolic dysfunction in women with PCOS. Moreover, in a recent Mendelian randomization study, gene variants associated with high bioavailable (unbound) circulating T levels were also linked with PCOS and type 2 diabetes [ 78 ], providing an additional causal role for female hyperandrogenism in the onset of both disorders.…”

Section: Introductionmentioning

confidence: 99%

Polycystic ovary syndrome as a plausible evolutionary outcome of metabolic adaptation

Dumesic

Padmanabhan

Chazenbalk

et al. 2022

Reprod Biol Endocrinol

View full text Add to dashboard Cite

As a common endocrinopathy of reproductive-aged women, polycystic ovary syndrome (PCOS) is characterized by hyperandrogenism, oligo-anovulation and polycystic ovarian morphology. It is linked with insulin resistance through preferential abdominal fat accumulation that is worsened by obesity. Over the past two millennia, menstrual irregularity, male-type habitus and sub-infertility have been described in women and confirm that these clinical features of PCOS were common in antiquity. Recent findings in normal-weight hyperandrogenic PCOS women show that exaggerated lipid accumulation by subcutaneous (SC) abdominal stem cells during development to adipocytes in vitro occurs in combination with reduced insulin sensitivity and preferential accumulation of highly-lipolytic intra-abdominal fat in vivo. This PCOS phenotype may be an evolutionary metabolic adaptation to balance energy storage with glucose availability and fatty acid oxidation for optimal energy use during reproduction. This review integrates fundamental endocrine-metabolic changes in healthy, normal-weight PCOS women with similar PCOS-like traits present in animal models in which tissue differentiation is completed during fetal life as in humans to support the evolutionary concept that PCOS has common ancestral and developmental origins.

show abstract

Section: Introductionmentioning

confidence: 99%

Polycystic ovary syndrome as a plausible evolutionary outcome of metabolic adaptation

Dumesic

Padmanabhan

Chazenbalk

et al. 2022

Reprod Biol Endocrinol

View full text Add to dashboard Cite

show abstract

“…The reality is that a C/T polymorphism in the tyrosine kinase domain of INSR gene can be a susceptible variant for PCOS ( Table 2 ). Furthermore, the rs2059807 and rs1799817 in INSR gene were significantly associated with IR in PCOS women in different populations [ 74 , 78 – 80 ]. In fact, INSR mediates the effect of insulin resistance on PCOS.…”

Section: Resultsmentioning

confidence: 99%

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

et al. 2021

View full text Add to dashboard Cite

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.

show abstract

“…In addition to epigenetic studies, many studies have been conducted to decipher the genetic nature of PCOS. In addition, a number of studies have looked at the link between significant clinical aspects of PCOS and GWAS-identified variants in the last several years [ 25 , 26 ]. The goal of the PCOS GWAS loci analysis is to provide insight on the mechanism by which the risk of SNPs may impact the aetiology of PCOS status and, ultimately, to improve treatment outcomes.…”

Section: Introductionmentioning

confidence: 99%

“…Following these studies, it appears that the genes DENND1A and TOX3, as well as the genes LHCGR, AMH, AMHR2, THADA, and INSR, are the most important genes in the susceptibility of PCOS. Genetic variations in the previously mentioned genes may be involved in several pathways, including insulin resistance, the dysregulation of androgen and gonadotrophins, and metabolic disorder-related pathways in PCOS pathogenesis [ 25 , 26 , 27 ]. There is ample evidence that polycystic ovary syndrome is an intrinsic syndrome, and in most of its clinical symptoms such as obesity and diabetes, traces of genetic variation might be seen [ 28 ].…”

Section: Introductionmentioning

confidence: 99%

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

Heidarzadehpilehrood

Pirhoushiaran

Abdollahzadeh

et al. 2022

Genes

View full text Add to dashboard Cite

Polycystic ovary syndrome is a multifactorial condition associated with reproductive and endocrine organs and might cause infertility and metabolic abnormalities in childbearing age. PCOS seems to be a multifactorial disorder resulting from the combination of several genetic and environmental factors. Little research has been conducted to date on the impact of polymorphisms in infertility. We aim to review the appearance of polymorphisms in females of diverse ethnicities and their effect on infertility in the population with polycystic ovary syndrome. There have been numerous reports of the importance of the steroidogenesis pathway and genetic variants in PCOS pathogenesis. The most important genes that play a role in the aetiology of PCOS are CYP11A1, CYP17A1, and CYP19A1. We evaluated the occurrence of polymorphisms in various ethnicities in the CYP11A1, CYP17A1, and CYP19A1 genes and their efficacy on increasing PCOS risk with infertility. Our findings revealed that polymorphisms in various ethnicities are associated with the risk of PCOS with infertility. Although conflicting results regarding CYP11A1, CYP17A1, and CYP19A1 polymorphisms and their influence on PCOS with infertility have been reported in a small number of papers, the authors feel this may be attributable to the sample size and ethnic composition of the examined populations. In conclusion, our study strongly suggests that the CYP11A1, CYP17A1, and CYP19A1 genes might significantly enhance the probability of developing PCOS with infertility.

show abstract

PCOS-GWAS Susceptibility Variants in THADA, INSR, TOX3, and DENND1A Are Associated With Metabolic Syndrome or Insulin Resistance in Women With PCOS

Cited by 42 publications

References 48 publications

Polycystic ovary syndrome as a plausible evolutionary outcome of metabolic adaptation

Polycystic ovary syndrome as a plausible evolutionary outcome of metabolic adaptation

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

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

Contact Info

Product

Resources

About