title: Androgen receptor CAG repeats length polymorphism and the risk of polycystic ovarian syndrome (PCOS).
abstract: 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%, 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: CSIR-Central Drug Research Institute, Lucknow, India.
authors.forename: Singh
authors.initials: S
authors.lastname: Rajender
authors.forename: Silas Justin
authors.initials: SJ
authors.lastname: Carlus
authors.forename: Sandeep Kumar
authors.initials: SK
authors.lastname: Bansal
authors.forename: Mahendra Pal Singh
authors.initials: MP
authors.lastname: Negi
authors.forename: Mahendra Pratap Singh
authors.initials: MP
authors.lastname: Negi
authors.forename: Nirmala
authors.initials: N
authors.lastname: Sadasivam
authors.forename: Muthusamy Narayanan
authors.initials: MN
authors.lastname: Sadasivam
authors.forename: Kumarasamy
authors.initials: K
authors.lastname: Thangaraj
mesh_terms: D000328:Adult; D000483:Alleles; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D017588:Hyperandrogenism / Q000235:genetics*; D008875:Middle Aged; D011085:Polycystic Ovary Syndrome / Q000235:genetics* / Q000378:metabolism; D011110:Polymorphism, Genetic; D011944:Receptors, Androgen / Q000235:genetics* / Q000378:metabolism; D018911:Trinucleotide Repeats
chemical_list: D011944:Receptors, Androgen