Androgen Receptor CAG Repeat Polymorphism and Epigenetic Influence among the South Indian Women with Polycystic Ovary Syndrome

Dasgupta, Shilpi; Sirisha, P.; Neelaveni, K; Anuradha, K; Reddy, Alla G.; Thangaraj, Kumarasamy; Reddy, B. Mohan

doi:10.1371/journal.pone.0012401

Cited by 44 publications

(53 citation statements)

References 21 publications

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“…35 Although the association of AR activity with CAG polymorphism and XCI has been extensively studied, they have produced conflicting results. 10,11,13,15,[17][18][19]21,22,36,37 There is little information on AR coregulators in the pathogenesis of PCOS, although recent advances in molecular biology have identified several AR coregulators that modulate the androgen action via cross talk with AR. 35,38 The dependency of the AR on its coregulators suggests a key role for these regulatory molecules in the development and maintenance of disorders associated with hyperandrogenism in humans.…”

Section: Discussionmentioning

confidence: 99%

Androgen Receptor Coregulator CTBP1-AS Is Associated With Polycystic Ovary Syndrome in Chinese Women: A Preliminary Study

et al. 2015

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Polycystic ovary syndrome (PCOS) is currently considered a predominantly hyperandrogenic syndrome. In theory, hyperandrogenism can be caused by high level of testosterone (T) as well as by enhanced androgen receptor (AR) activity. C-Terminal binding protein 1 antisense (CTBP1-AS) was a novel long noncoding RNA (lncRNA) to regulate AR activity. In this study, we found that expression level of CTBP1-AS in peripheral blood leukocytes was significantly higher in women with PCOS than that in controls after adjustment for age and body mass index (BMI). Individuals having higher expression of CTBP1-AS had significantly greater disease risk than those having lower expression. We also identified expression of CTBP1-AS as an independent risk factor for PCOS. A positive correlation was observed between the CTBP1-AS expression and the total T (TT) concentration either unadjusted or after adjusting for age, BMI, and homeostatic model assessment insulin resistance. Taken together, our current study presented the first evidence that the lncRNA CTBP1-AS, a novel AR modulator, is associated with PCOS in Chinese population and established the possibility that abnormal CTBP1-AS expression is a risk factor for PCOS and it is a predictor of variability in serum TT level in Chinese women with PCOS.

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Section: Discussionmentioning

confidence: 99%

Androgen Receptor Coregulator CTBP1-AS Is Associated With Polycystic Ovary Syndrome in Chinese Women: A Preliminary Study

et al. 2015

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“…After carefully reviewing, finally, ten studies [23][24][25][26][27][28][29][30][31][32] and current article with 1,536 PCOS patients and 1,807 controls were included in this metaanalysis. The flow diagram of study selection was presented in Fig.…”

Section: Eligible Studymentioning

confidence: 99%

“…Thus a large number of studies have been conducted to investigate the relationship between AR gene CAG repeats and PCOS, however, with inconsistent results [19,[23][24][25][26][27][28][29][30][31][32][33]. Based on these inconsistent results, we performed current study to research this association and meta-analysis.…”

Section: Introductionmentioning

confidence: 99%

The association between androgen receptor gene CAG polymorphism and polycystic ovary syndrome: a case-control study and meta-analysis

Peng

Xie

Guo

et al. 2014

J Assist Reprod Genet

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Purpose Many studies have been carried out to confirm the relationship between androgen receptor gene CAG repeat polymorphism and polycystic ovary syndrome (PCOS), without consistent results. Hence we conducted the current study to research this relationship. Methods 224 Chinese Han women with PCOS and 223 in vitro fertilization and embryo transplantation (IVF-ET) infertile women with tubal factor or male infertility served as the controls were recruited in our study. PCR-based assays were applied to genotype the (CAG) n repeat alleles. A metaanalysis including 1,536 PCOS patients and 1,807 controls was conducted to produce a pooled estimate. Results We observed that the CAG bi-allelic mean lengths were similar in PCOS patients and controls (22.65±2.5 vs. 23.09±2.1, P=0.116). When CAG bi-allelic were divided into two categories (mean repeats ≤22, >22), the short AR-CAG bi-allelic showed more frequent in PCOS group than in controls (56.25 % vs 29.14 %, P<0.001). Further analysis presented that, in PCOS, there was a lower mean CAG repeat lengths in mean bi-allelic lengths (22.3±2.5 vs. 23.9±2.2, P= 0.008) and long bi-allelic lengths (24.3±1.4 vs. 25.9±1.6, P= 0.05) among patients with testosterone less than 0.7 ng/ml compared with those whose testosterone was more than 0.7 ng/ml. Besides, the testosterone were positively correlated with the CAG polymorphism (r=0.237, P=0.008), which accorded with our meta-analysis results. Conclusions The distribution of AR-CAG allele differed between PCOS patients and controls, and polymorphism of CAG repeat lengths may contribute to hyperandrogenism in PCOS.

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“…Exon 1 contains a polymorphic sequence of CAG repeat which encodes polyglutamine stretches of AR transactivation domain [15,16]. Evidence implies that CAG number is inversely linked to the transcriptional activity of AR [17,18], thus greater number of CAG repeats results in decreased testicular atrophy and sperm production.…”

Section: Cag Androgen Receptormentioning

confidence: 99%

Polycystic Ovary Syndrome: Conditions, Genetics and Current Cure

Qamar¹

2016

EMIJ

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Polycystic ovary syndrome (PCOS) is one of the general disorders of endocrine system affecting around 7 to 10% of reproductive age women and is the leading cause of Female infertility [1]. Polycystic ovary syndrome has characteristic polycystic ovaries, hyperandrogenism and anovulation. It is a wide reproductive disorder that umbrellas many related health conditions such as obesity, type 2 diabetes, insulin resistance, cardiovascular disease, and PCOS can be related with metabolic disorders in the first-line family members [1,2]. PCOS has Insulin resistance as key pathophysiology and dyslipidemia in women with PCOS can hence be found in the insulin resistant state [3]. Despite the increasing cases of this syndrome and decades of research, the cause of PCOS is incompletely unknown, but various studies describe it as an internal ovarian abnormality. PCOS has no medicinal cure [4], but oral contraceptive pills (OCPs), anti-androgens and insulin controlling drug like metformin can help with improving the regularity of periods and other metabolic conditions [5]. In this review, the conditions in PCOS, genetic factors and genes involved, current treatments and future perspective of PCOS has been briefly discussed.

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Androgen Receptor CAG Repeat Polymorphism and Epigenetic Influence among the South Indian Women with Polycystic Ovary Syndrome

Cited by 44 publications

References 21 publications

Androgen Receptor Coregulator CTBP1-AS Is Associated With Polycystic Ovary Syndrome in Chinese Women: A Preliminary Study

Androgen Receptor Coregulator CTBP1-AS Is Associated With Polycystic Ovary Syndrome in Chinese Women: A Preliminary Study

The association between androgen receptor gene CAG polymorphism and polycystic ovary syndrome: a case-control study and meta-analysis

Polycystic Ovary Syndrome: Conditions, Genetics and Current Cure

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