Dataset Information

Association of androgen receptor CAG repeat polymorphism and polycystic ovary syndrome.

ABSTRACT:

Context

Genetically determined heightened androgen sensitivity may influence the phenotype of polycystic ovary syndrome (PCOS). To date, studies of the androgen receptor exon 1 polymorphic CAG repeat have produced conflicting results in PCOS.

Objective

We tested the hypothesis that a lower number of CAG repeats is associated with increased odds of PCOS. We also compared X-chromosome inactivation between cases and controls.

Design

Women with and without PCOS were genotyped for the CAG repeat and assessed for X-chromosome methylation. Association analyses were performed.

Setting

Subjects were recruited from the reproductive endocrinology clinic at the University of Alabama at Birmingham; controls were recruited from the surrounding community. Genotyping took place at Cedars-Sinai Medical Center in Los Angeles.

Participants

Participants included 330 women with PCOS and 289 controls (77% white, 23% black).

Main measurements

Androgen receptor genotype, X-chromosome methylation, and phenotyping for PCOS were measured.

Results

A smaller biallelic mean of CAG repeats was associated with increased odds of PCOS. X-chromosome inactivation was not different comparing cases with controls; however, in the subset with nonrandom inactivation, the chromosome bearing the shorter CAG allele was preferentially active in PCOS women.

Conclusions

Association of shorter CAG repeats with PCOS is consistent with in vitro functional studies demonstrating higher activity of androgen receptors expressed from alleles with fewer CAG repeats, suggesting inherited alteration in androgen sensitivity may contribute to PCOS. In some women, such heightened sensitivity may also result from preferential expression of androgen receptors with shorter alleles. Thus, genetic and epigenetic changes may be involved in the pathogenesis of PCOS.

SUBMITTER: Shah NA

PROVIDER: S-EPMC2386276 | biostudies-literature | 2008 May

REPOSITORIES: biostudies-literature

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Publications

Association of androgen receptor CAG repeat polymorphism and polycystic ovary syndrome.

Shah Nissar A NA Antoine Heath J HJ Pall Marita M Taylor Kent D KD Azziz Ricardo R Goodarzi Mark O MO

The Journal of clinical endocrinology and metabolism 20080226 5

<h4>Context</h4>Genetically determined heightened androgen sensitivity may influence the phenotype of polycystic ovary syndrome (PCOS). To date, studies of the androgen receptor exon 1 polymorphic CAG repeat have produced conflicting results in PCOS.<h4>Objective</h4>We tested the hypothesis that a lower number of CAG repeats is associated with increased odds of PCOS. We also compared X-chromosome inactivation between cases and controls.<h4>Design</h4>Women with and without PCOS were genotyped f ...[more]

PMID: 18303071

Similar Datasets

Project description:ObjectivePolycystic 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.MethodsCAG 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.ResultsCAG 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%, χ(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. Meta-analysis also showed no significant correlation between CAG length and PCOS risk, except a minor over-representation of short CAG alleles in the cases.ConclusionCAG 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.

Dataset Information

Association of androgen receptor CAG repeat polymorphism and polycystic ovary syndrome.

Context

Objective

Design

Setting

Participants

Main measurements

Results

Conclusions

Publications

Association of androgen receptor CAG repeat polymorphism and polycystic ovary syndrome.

Similar Datasets

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