Role of the CAG repeat polymorphism of the androgen receptor gene in polycystic ovary syndrome (PCOS)

Exp Clin Endocrinol Diabetes. 2012 Feb;120(2):73-9. doi: 10.1055/s-0031-1291343. Epub 2011 Nov 8.

Abstract

Background: Polycystic ovary syndrome (PCOS) is a frequent heterogenic disorder with a familial background. Androgenic effects, determining the clinical features of the syndrome, are mediated by the androgen receptor (AR), whose activity is modulated by a genetic polymorphism. We investigated the role of the CAG repeat polymorphism of the androgen receptor in PCOS.

Methods: In the infertility unit of a university clinic, 72 PCOS patients were compared with 179 ovulatory controls undergoing a standardized diagnostic work-up. The number of CAG repeats was determined by PCR, labelling with IR-800 and PAGE. X-chromosome inactivation was assessed by a methylation-sensitive assay.

Results: Compared to controls, PCOS patients displayed a shorter mean CAG repeat length, encoding for higher AR activity (P=0.001). CAG repeat length correlated inversely with oligomenorrhea, a central androgen dependent feature of the syndrome (P=0.005). In a binomial regression analysis including BMI, LH and free testosterone, CAG repeat length was identified as an independent risk factor for PCOS (P=0.002).

Conclusions: The CAG repeat polymorphism could constitute one of the genetic factors modulating the syndrome's phenotype, contributing to its clinical heterogeneity and associated metabolic consequences.

MeSH terms

  • Adult
  • Base Sequence
  • Case-Control Studies
  • Female
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Humans
  • Menstrual Cycle / genetics
  • Menstrual Cycle / physiology
  • Phenotype
  • Polycystic Ovary Syndrome / etiology
  • Polycystic Ovary Syndrome / genetics*
  • Polycystic Ovary Syndrome / metabolism
  • Polymorphism, Genetic / physiology
  • Receptors, Androgen / genetics*
  • Receptors, Androgen / physiology
  • Risk Factors
  • Trinucleotide Repeat Expansion / genetics*
  • X Chromosome Inactivation / physiology
  • Young Adult

Substances

  • Receptors, Androgen