Polymorphic CAG repeat in the androgen receptor gene in polycystic ovary syndrome patients

Xia, Yijun; Che, Yena; Zhang, Xinlin; Zhang, Chengwei; Cao, Yunxia; Wang, Wenjun; Xu, Pei; Wu, Xiaoke; Yi, Long; Gao, Qian; Wang, Yong

doi:10.3892/mmr.2012.789

Cited by 11 publications

(5 citation statements)

References 30 publications

(28 reference statements)

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“…Inconsistent associations of the differences in number of CAG repeats in exon 1 have been reported with PCOS prevalence. It has later been ascertained that short AR CAG repeats were more frequent in PCOS cases and may possibly be linked to PCOS onset in both Chinese and Caucasian populations [ 100 , 105 – 108 ]. This may contribute to the inherent hyperandrogenic phenotype commonly seen in women with PCOS by increasing AR activity and enhancing androgen sensitivity to even low circulating levels of testosterone, thereby promoting hirsutism, acne, and irregular cycles [ 106 , 109 ].…”

Section: Genetics Of Pcosmentioning

confidence: 99%

Genetic Variants Associated with Hyperandrogenemia in PCOS Pathophysiology

Dadachanji

Shaikh

Mukherjee

2018

Genetics Research International

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Polycystic ovary syndrome is a multifactorial endocrine disorder whose pathophysiology baffles many researchers till today. This syndrome is typically characterized by anovulatory cycles and infertility, altered gonadotropin levels, obesity, and bulky multifollicular ovaries on ultrasound. Hyperandrogenism and insulin resistance are hallmark features of its complex pathophysiology. Hyperandrogenemia is a salient feature of PCOS and a major contributor to cosmetic anomalies including hirsutism, acne, and male pattern alopecia in affected women. Increased androgen levels may be intrinsic or aggravated by preexisting insulin resistance in women with PCOS. Studies have reported augmented ovarian steroidogenesis patterns attributed mainly to theca cell hypertrophy and altered expression of key enzymes in the steroidogenic pathway. Candidate gene studies have been performed in order to delineate the association of polymorphisms in genes, which encode enzymes in the intricate cascade of steroidogenesis or modulate the levels and action of circulating androgens, with risk of PCOS development and its related traits. However, inconsistent findings have impacted the emergence of a unanimously accepted genetic marker for PCOS susceptibility. In the current review, we have summarized the influence of polymorphisms in important androgen related genes in governing genetic predisposition to PCOS and its related metabolic and reproductive traits.

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Section: Genetics Of Pcosmentioning

confidence: 99%

Genetic Variants Associated with Hyperandrogenemia in PCOS Pathophysiology

Dadachanji

Shaikh

Mukherjee

2018

Genetics Research International

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“…Our analysis on a large sample size from South India found that the mean CAG length does not significantly differ between cases and controls; nevertheless a trend of higher frequency of extreme sized alleles in the cases in comparison to the controls was seen. Increased PCOS risk with short CAG is supported by an almost equal number of studies [9][10][11]22] as many studies deny any such correlation [7,[12][13][14][15][16]. At least one study suggested increased risk with an increase in CAG length [8].…”

Section: Discussionmentioning

confidence: 96%

“…Literature search retrieved twenty-two studies, of which only fifteen studies fulfilled the inclusion criteria. Among the remaining seven studies, two [11,22] were excluded due to lack of full text article, four [2,4,10,17] due to irrelevant data, and one [23] due to lack of information required for metaanalysis. For Shah et al (2008), we used two separate data sets (Black and White populations) in meta-analysis.…”

Section: Meta-analysismentioning

confidence: 99%

Correction: Androgen Receptor CAG Repeats Length Polymorphism and the Risk of Polycystic Ovarian Syndrome (PCOS)

Rajender¹,

Carlus²,

Negi³

et al. 2013

PLoS ONE

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Objective: Polycystic ovarian syndrome (PCOS) refers to an inheritable androgen excess disorder characterized by multiple small follicles located at the ovarian periphery. Hyperandrogenism in PCOS, and inverse correlation between androgen receptor (AR) CAG numbers and AR function, led us to hypothesize that CAG length variations may affect PCOS risk.Methods: CAG repeat region of 169 patients recruited following strictly defined Rotterdam (2003) inclusion criteria and that of 175 ethnically similar control samples, were analyzed. We also conducted a meta-analysis on the data taken from published studies, to generate a pooled estimate on 2194 cases and 2242 controls.Results: CAG bi-allelic mean length was between 8.5 and 24.5 (mean = 17.43, SD = 2.43) repeats in the controls and between 11 and 24 (mean = 17.39, SD = 2.29) repeats in the cases, without any significant difference between the two groups. Further, comparison of bi-allelic mean and its frequency distribution in three categories (short, moderate and long alleles) did not show any significant difference between controls and various case subgroups. Frequency distribution of bi-allelic mean in two categories (extreme and moderate alleles) showed over-representation of extreme sized alleles in the cases with marginally significant value (50.3% vs. 61.5%, x 2 = 4.41; P = 0.036), which turned insignificant upon applying Bonferroni correction for multiple comparisons. X-chromosome inactivation analysis showed no significant difference in the inactivation pattern of CAG alleles or in the comparison of weighed bi-allelic mean between cases and controls. Metaanalysis also showed no significant correlation between CAG length and PCOS risk, except a minor over-representation of short CAG alleles in the cases. Conclusion:CAG bi-allelic mean length did not differ between controls and cases/case sub-groups nor did the allele distribution. Over-representation of short/extreme-sized alleles in the cases may be a chance finding without any true association with PCOS risk.

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“…However, Mifsud et al found no significant differences between the anovulatory PCOS patients and controls in the distribution of the CAG repeats [88]. Xia et al reported that shorter alleles of the (CAG)n in the first exon of AR gene enhanced the PCOS susceptibility either by upregulating AR activity or resulting in hyperandrogenism in the PCOS patients from China [89] and these findings were also corroborated in the Caucasian population [90]. Rajender et al reported that CAG bi-allelic mean length and allele distribution did not differ between controls and cases in PCOS cases from India [91].…”

Section: Ar (Androgen Receptor) Genementioning

confidence: 99%

Genetics and Epigenetics of Polycystic Ovary Syndrome

Prakash Goud Ponnam,

Paul

2024

Obstetrics and Gynecology

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Polycystic ovary syndrome (PCOS) is one of the most common endocrinological and reproductive disorders in women of reproductive age with a global prevalence rate of 5–20%. It is a clinically and genetically heterogeneous disorder. There have been multiple reports from independent research groups from different ethnicities that a variety of factors, including genetics and epigenetics, significantly contribute to the etiopathogenesis of PCOS. GWAS, twin studies, and genotype-phenotype association studies have resulted in the identification of more than a dozen candidate genes/loci with PCOS. In the proposed book chapter, we aim to provide insight and discuss the role of various genetic and epigenetic elements that are responsible for PCOS globally and in India. This book chapter should serve as a reference to all the basic researchers and healthcare professionals on the genetics and epigenetics of PCOS.

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Polymorphic CAG repeat in the androgen receptor gene in polycystic ovary syndrome patients

Cited by 11 publications

References 30 publications

Genetic Variants Associated with Hyperandrogenemia in PCOS Pathophysiology

Genetic Variants Associated with Hyperandrogenemia in PCOS Pathophysiology

Correction: Androgen Receptor CAG Repeats Length Polymorphism and the Risk of Polycystic Ovarian Syndrome (PCOS)

Genetics and Epigenetics of Polycystic Ovary Syndrome

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