Schüring A N, Welp A, Gromoll J, Zitzmann M, Sonntag B, Nieschlag E, Greb R R, Kiesel L
Department of Obstetrics and Gynecology, Münster University Hospital, Münster, Germany.
Exp Clin Endocrinol Diabetes. 2012 Feb;120(2):73-9. doi: 10.1055/s-0031-1291343. Epub 2011 Nov 8.
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.
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.
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).
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.
多囊卵巢综合征（PCOS）是一种常见的具有家族背景的异质性疾病。雄激素作用决定了该综合征的临床特征，由雄激素受体（AR）介导，其活性受基因多态性调节。我们研究了雄激素受体的CAG重复多态性在PCOS中的作用。
在一所大学诊所的不孕不育科，将72例PCOS患者与179例接受标准化诊断检查的排卵正常对照者进行比较。通过PCR、用IR-800标记和聚丙烯酰胺凝胶电泳（PAGE）确定CAG重复序列的数量。通过甲基化敏感试验评估X染色体失活情况。
与对照组相比，PCOS患者的平均CAG重复长度较短，编码更高的AR活性（P = 0.001）。CAG重复长度与月经过少呈负相关，月经过少是该综合征的一个主要雄激素依赖特征（P = 0.005）。在包括体重指数（BMI）、促黄体生成素（LH）和游离睾酮的二项回归分析中，CAG重复长度被确定为PCOS的独立危险因素（P = 0.002）。
CAG重复多态性可能是调节该综合征表型的遗传因素之一，导致其临床异质性及相关代谢后果。
