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

<div><p>Objective</p><p>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.</p><p>Methods</p><p>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.</p><p>Results</p><p>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%, χ² = 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.</p><p>Conclusion</p><p>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.</p></div

Frequency distribution (%) of CAG bi-allelic mean length in two CAG categories (extreme and moderate).

*<p>Comparison of categorical variable between groups was done by <b>χ²</b>test.</p

Figure 4

<p>. <b>XCI analysis.</b> X-chromosome inactivation analysis showing random, non-random, and skewed inactivation.</p

Frequency distribution (%) of CAG bi-allelic mean length in three CAG length categories (short, moderate, and long).

*<p>Comparison of categorical variable between groups was done by <b>χ²</b>test.</p

Demographic features of PCOS group.

<p>Demographic features of PCOS group.</p

Summary of meta-analysis results.

*<p>indicates Egger’s regresstion test two tailed p value.</p

Published data extracted for meta-analysis.

*<p>Shown only when P value was manually fed into the software.</p

CAG bi-allelic mean distribution.

<p>Comparison of bi-allelic mean data in two CAG categories (extreme and moderate alleles) between controls and cases (a), and between controls and case subgroups based on obesity (b), androgenism (c), and hirsutism (d).</p

Comparison of CAG bi-allelic mean length between controls and case subgroups.

*<p>For comparison between two groups and three groups, student’s‘t’ test and ANOVA was done, respectively.</p

CAG allele distribution.

<p>Frequency distribution of CAG alleles in the PCOS cases and control samples (upper panel), and in obese, non-obese and control samples (lower panel).</p