Polymorphism of CAG and GGN repeats of androgen receptor gene in women with polycystic ovary syndrome

Yuan, Chun Su; Gao, Chao; Qian, Yi; Liu, Ying; Jiang, Shi‐Wen; Cui, Yugui; Liu, Jiayin

doi:10.1016/j.rbmo.2015.09.007

Cited by 11 publications

(8 citation statements)

References 28 publications

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“…It has reach a consensus that overproduction of ovarian androgen is a pivotal pathologic feature of PCOS. [16,17] Series of intracellular and extracellular signaling pathways involved in PCOS pathogenesis have been impressed by steroidogenesis and androgen. [18,19] Prenatal androgen exposure and adolescent studies suggest that early androgen excess acts as an initiating factor of PCOS, but it still needs to confirm these hypothesis relying on convictive evidences.…”

Section: Discussionmentioning

confidence: 99%

Promoter methylation of yes-associated protein (YAP1) gene in polycystic ovary syndrome

et al. 2017

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Background:DNA methylation modification has been proved to influence the phenotype of polycystic ovary syndrome (PCOS). Genome-wide association studies (GWAS) demonstrate that yes-associated protein (YAP1) genetic sites are associated with PCOS. The study aims to detect the methylation status of YAP1 promoter in ovary granulosa cells (GCs) of PCOS patients and explore novel therapeutic targets for PCOS.Methods:Randomized controlled trial was applied and a total of 72 women were included in the study, including 36 cases of PCOS patients and 36 cases of health controls. Ovary GCs were extracted from in vitro fertilization embryo transfer. Methylation status of YAP1 promoter was detected by bisulfite sequencing PCR (BSP). Protein and mRNA expression of YAP1 were measured by western blotting and real-time quantitate PCR.Results:Overall methylation level of YAP1 promoter region from PCOS group was significantly lower than that from control group. CpG sites analysis revealed that 12 sites (−443, −431, −403, −371, −331, −120, −49, −5, +1, +9, +15, +22) were significantly hypomethylated in women with PCOS (P < 0.05). A significant upregulation of YAP1 mRNA and protein expression levels was observed. Testosterone concentration could alleviate the methylation status and demonstrate obvious dose–dependent relation.Conclusion:Our research achievements manifest that hypomethylation of YAP1 promoter promotes the YAP1 expression, which plays a key role in the pathogenesis and accelerate PCOS.

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Section: Discussionmentioning

confidence: 99%

Promoter methylation of yes-associated protein (YAP1) gene in polycystic ovary syndrome

et al. 2017

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“…Meta-analyses examining the relationship between CAG repeat lengths at AR and PCOS risk have concluded that they may not be major determining factors in PCOS etiology [ 111 , 119 , 120 ]. Apart from CAG repeat, other groups have concluded that a GGN repeat polymorphism and rs6152G/A polymorphism were also significantly associated with PCOS in Chinese women [ 121 , 122 ]. Thus, AR polymorphisms may exacerbate the hyperandrogenic phenotype of women with PCOS.…”

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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“…Hpall digests only unmethylated (active) DNA segments, leaving the undigested methylated (inactive) DNA template intact for amplification. Digested and mock-digested genomic DNA from the same woman were amplified using PCR with primers, as previously described [ 36 ]. The forward primer was 5(6)-carboxyfluorescein-labelled.…”

Section: Methodsmentioning

confidence: 99%

Investigation of the role of X chromosome inactivation and androgen receptor CAG repeat polymorphisms in patients with recurrent pregnancy loss: a prospective case–control study

Sui

Zhang

et al. 2022

BMC Pregnancy Childbirth

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Background Previous research has revealed that skewed X chromosome inactivation (SXCI) and androgen receptor (AR) CAG polymorphisms are associated with increased risk of recurrent pregnancy loss (RPL); however, the results are conflicting, and the underlying mechanisms remain unclear. This study investigated the role of SXCI and AR CAG polymorphisms in patients with RPL and explored whether the underlying mechanisms were related to the ovarian reserve and preimplantation embryo aneuploidy. Methods This was a prospective case-control study carried out in a tertiary hospital-based reproductive medicine center. An external validation RPL cohort was recruited during the study period. Data on baseline and cycle characteristics were collected. X-chromosome inactivation (XCI) was measured using a human AR assay. AR polymorphisms were assessed using quantitative fluorescent polymerase chain reactions and direct sequencing. Blastocysts of the patients with RPL were tested by single nucleotide polymorphism microarray based preimplantation genetic testing for aneuploidy. Results In total, 131 patients with idiopathic RPL and 126 controls were included for the case-control study. Patients with RPL exhibited a significantly more skewed XCI distribution pattern (67.71 ± 10.50 vs. 64.22 ± 10.62, p = 0.011), as well as significantly shorter bi-allelic mean (18.56 ± 1.97 vs. 19.34 ± 2.38, p = 0.005) and X-weighted bi-allelic mean (18.46 ± 2.02 vs. 19.38 ± 2.53, p = 0.001) of AR CAG repeats. Multivariate logistic regression models indicated that CAG repeat < 20, SXCI, and duration of stimulation were independently associated with the risk of RPL. However, SXCI and AR CAG polymorphisms were not associated with ovarian reserve or preimplantation embryo aneuploidy in the RPL group, and the same results were attained in a separate validation cohort of 363 patients with RPL. Conclusion SXCI and AR CAG polymorphisms are related to RPL; however, these two factors do not lead to RPL by affecting the ovarian reserve or increasing embryo aneuploidy. The roles of SXCI and AR CAG in RPL may involve other mechanisms that require further investigation. Trial registration: NCT02504281, https://www.clinicaltrials.gov (Date of registration, 21/07/2015; date of enrolment of the first subject, 30/07/2015).

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Polymorphism of CAG and GGN repeats of androgen receptor gene in women with polycystic ovary syndrome

Cited by 11 publications

References 28 publications

Promoter methylation of yes-associated protein (YAP1) gene in polycystic ovary syndrome

Promoter methylation of yes-associated protein (YAP1) gene in polycystic ovary syndrome

Genetic Variants Associated with Hyperandrogenemia in PCOS Pathophysiology

Investigation of the role of X chromosome inactivation and androgen receptor CAG repeat polymorphisms in patients with recurrent pregnancy loss: a prospective case–control study

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