Department of Obstetrics and Gynecology, Virginia Commonwealth University School of Medicine, Richmond, VA 23298, USA.
Mol Cell Endocrinol. 2012 Mar 5;350(1):72-7. doi: 10.1016/j.mce.2011.11.022. Epub 2011 Dec 8.
Polycystic ovary syndrome (PCOS) is an endocrine disorder that affects 5-8% of reproductive age women. The primary features of PCOS are hyperandrogenemia, chronic anovulation and infertility. It has been suggested that defects in ovarian steroid metabolism contribute to the follicular growth arrest and abnormal production of ovarian steroid hormones that are characteristic of PCOS. 2-Methoxyestradiol (2-ME) is formed by the action of catechol-O-methyltransferase (COMT) on 2-hydroxyestradiol. COMT expression is increased in the follicles and ovarian stroma of women with PCOS. Moreover, 2-ME decreases granulosa cell proliferation and steroidogenesis, raising the possibility that ovarian dysfunction associated with PCOS is due, in part, to increased synthesis of 2-ME resulting from increased COMT activity. Four single-nucleotide polymorphisms (SNPs) (rs6269, rs4633, rs4818, rs4680) in the COMT gene characterize haplotypes, which are associated with large variations in COMT enzymatic activity. The aim of this study was to determine whether individual COMT SNPs and the COMT haplotypes are associated with PCOS using a family-based test of association and linkage. Additionally, we examined the relationships between COMT SNPs and haplotypes with quantitative variables usually assessed in the evaluation of women with PCOS. There were no significant correlations between genotype and total testosterone, non-SHBG bound testosterone and BMI. However, we found that the prolactin level in women with PCOS varied significantly with COMT haplotype, and suggest that this association reflects a genetic factor influencing the stress response. Our findings suggest that common variants and haplotypes of the COMT gene are not major contributors to risk for PCOS, but that COMT genotype may influence prolactin levels.
多囊卵巢综合征(PCOS)是一种影响 5-8%育龄妇女的内分泌疾病。PCOS 的主要特征是高雄激素血症、慢性无排卵和不孕。有人认为,卵巢甾体代谢缺陷导致卵泡生长停滞和卵巢甾体激素异常产生,这是 PCOS 的特征。2-甲氧基雌二醇(2-ME)是儿茶酚-O-甲基转移酶(COMT)作用于 2-羟雌二醇形成的。PCOS 妇女的卵泡和卵巢基质中 COMT 表达增加。此外,2-ME 可降低颗粒细胞增殖和甾体生成,这提示与 PCOS 相关的卵巢功能障碍部分归因于 COMT 活性增加导致的 2-ME 合成增加。COMT 基因中的 4 个单核苷酸多态性(SNP)(rs6269、rs4633、rs4818、rs4680)特征性地构成单倍型,与 COMT 酶活性的巨大差异相关。本研究旨在使用基于家族的关联和连锁检验来确定 COMT SNP 和 COMT 单倍型是否与 PCOS 相关。此外,我们还检查了 COMT SNP 和单倍型与 PCOS 评估中通常评估的定量变量之间的关系。基因型与总睾酮、非 SHBG 结合睾酮和 BMI 之间无显著相关性。然而,我们发现 PCOS 妇女的催乳素水平与 COMT 单倍型显著相关,提示这种关联反映了影响应激反应的遗传因素。我们的研究结果表明,COMT 基因的常见变体和单倍型不是 PCOS 风险的主要因素,但 COMT 基因型可能影响催乳素水平。