Variants in the 5α-reductase type 1 and type 2 genes are associated with polycystic ovary syndrome and the severity of hirsutism in affected women
Variants in the 5α-reductase type 1 and type 2 genes are associated with polycystic ovary syndrome and the severity of hirsutism in affected women
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DOI：
10.1210/jc.2006-0227
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发表时间：
2006-10-01
影响因子：
5.8
通讯作者：
Azziz, Ricardo
中科院分区：
文献类型：
--
作者：
Goodarzi, Mark O.;Shah, Nissar A.;Azziz, Ricardo
背景：尽管双氢睾酮在雄激素作用中很重要，但5 α -还原酶（SRD5A1和SRD5A2）的两种异构体基因多态性尚未被评估为多囊卵巢综合征（PCOS）的危险因素。目的：本研究的目的是验证SRD5A1和SRD5A2基因的单倍型是多囊卵巢综合征和多毛症严重程度的危险因素的假设。设计：对PCOS和对照组进行SRD5A1 7个单核苷酸多态性和SRD5A2 8个单核苷酸多态性的基因分型。测定单倍型并检测其与PCOS诊断和组分表型的相关性。背景：研究对象从阿拉巴马大学伯明翰分校生殖内分泌诊所招募；对照对象从周围社区招募。基因分型在洛杉矶的雪松-西奈医疗中心进行。参与者：共有287名白人多囊卵巢综合征女性和187名对照组参与。主要测量方法：评估SRD5A1和SRD5A2基因型、定量多毛评分、激素和代谢表型。结果：两个基因内的单倍型与PCOS风险相关。SRD5A2 Val89Leu变异的Leu等位基因与PCOS的保护作用相关；已知该等位基因可适度降低5 α -还原酶活性。SRD5A1单倍型而非SRD5A2单倍型也与受影响女性多毛程度相关。结论：本研究提供了遗传证据，表明5 α -还原酶的两种亚型在多囊卵巢综合征的发病机制中都起着重要作用。只有SRD5A1单倍型与多毛症相关，这表明只有这种同型在毛囊中是重要的。
Context: Despite the importance of dihydrotestosterone in androgen action, polymorphisms in the genes for the two isoforms of 5 alpha-reductase (SRD5A1 and SRD5A2) have not been evaluated as risk factors for polycystic ovary syndrome (PCOS).Objective: The objective of the study was to test the hypothesis that haplotypes in the SRD5A1 and SRD5A2 genes are risk factors for PCOS and the severity of hirsutism in affected women.Design: PCOS and control subjects were genotyped for seven single-nucleotide polymorphisms in SRD5A1 and eight single-nucleotide polymorphisms in SRD5A2. Haplotypes were determined and tested for association with PCOS diagnosis and component phenotypes.Setting: Subjects were recruited from the reproductive endocrinology clinic at the University of Alabama at Birmingham; control subjects were recruited from the general surrounding community. Genotyping took place at Cedars-Sinai Medical Center in Los Angeles.Participants: A total of 287 White women with PCOS and 187 controls participated. Main Measurements: SRD5A1 and SRD5A2 genotype, quantitative hirsutism score, and hormonal and metabolic phenotypes were assessed.Results: Haplotypes within both genes were associated with PCOS risk. The Leu allele of the Val89Leu variant in SRD5A2 was associated with protection against PCOS; this allele is known to modestly reduce 5 alpha-reductase activity. Haplotypes in SRD5A1 but not SRD5A2 were also associated with the degree of hirsutism in affected women.Conclusions: This study presents genetic evidence suggesting an important role of both isoforms of 5 alpha-reductase in the pathogenesis of PCOS. That only SRD5A1 haplotypes were associated with hirsutism suggests that only this isoform is important in the hair follicle.