Role of the CAG Repeat Polymorphism of the Androgen Receptor Gene in Polycystic Ovary Syndrome (PCOS)

A. N. Schüring; A. Welp; J. Gromoll; M. Zitzmann; B. Sonntag; E. Nieschlag; R. R. Greb; L. Kiesel

doi:10.1055/s-0031-1291343

Experimental and Clinical Endocrinology & Diabetes, Table of Contents

Exp Clin Endocrinol Diabetes 2012; 120(02): 73-79
DOI: 10.1055/s-0031-1291343

Article

Role of the CAG Repeat Polymorphism of the Androgen Receptor Gene in Polycystic Ovary Syndrome (PCOS)

Authors

A. N. Schüring^*

¹Department of Obstetrics and Gynecology, Münster University Hospital, Münster, Germany
A. Welp^*

¹Department of Obstetrics and Gynecology, Münster University Hospital, Münster, Germany
J. Gromoll

²Institute of Reproductive Medicine, Münster University Hospital, Münster, Germany
M. Zitzmann

²Institute of Reproductive Medicine, Münster University Hospital, Münster, Germany
B. Sonntag

¹Department of Obstetrics and Gynecology, Münster University Hospital, Münster, Germany
E. Nieschlag

²Institute of Reproductive Medicine, Münster University Hospital, Münster, Germany
R. R. Greb

¹Department of Obstetrics and Gynecology, Münster University Hospital, Münster, Germany
L. Kiesel

¹Department of Obstetrics and Gynecology, Münster University Hospital, Münster, Germany

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.

Key words

polycystic ovary syndrome - hyperandrogenemia - luteinizing hormone - androgen receptor - genetic polymorphism

Full Text

References

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