Estrogen receptor α gene polymorphisms are associated with idiopathic premature ovarian failure
Estrogen receptor α gene polymorphisms are associated with idiopathic premature ovarian failure
复制标题
DOI：
10.1016/j.fertnstert.2007.03.008
复制
发表时间：
2008-02-01
影响因子：
6.7
通讯作者：
Robinson, Wendy P.
中科院分区：
文献类型：
--
作者：
Bretherick, Karla L.;Hanna, Courtney W.;Robinson, Wendy P.
目的：评估激素受体/结合蛋白变异在卵巢早衰 (POF) 遗传易感性中的作用。设计：病例对照研究。背景：学术界。患者：55 名 POF 患者、107 名来自普通人群的对照女性，以及 27 名 37 岁后已证明具有生育能力的对照女性。干预措施：无。主要结果指标：评估病例和对照的等位基因分布的遗传性结果：雄激素受体（AR）基因、雌激素受体β（ESR2）基因、性激素结合球蛋白（SHBG）基因和FSH受体（FSHR）基因的多态性等位基因分布在患者和对照之间没有差异。在雌激素受体 α (ESR1) 基因启动子的重复中，POF 患者比对照组有发烧 (< 18) 短重复等位基因 (P = .004) 与组合对照组相比。在 36.4% 的对照女性中发现了由两个短等位基因组成的基因型，但在 POF 患者中这一比例仅为 5.5%（与组合对照相比，P < 0.0001）。 ESR1 重复可能以简单的显性方式带来 POF 风险，其中长重复的携带者的相对风险为 9.7 (95% CI = 2.6 - 35.6)。结论：ESR1 基因的多态性与该患者群体中的 POF 相关，而 AR、ESR2、SHBG 和 FSHR 中的多态性则没有相关性。需要进一步的研究来在更大的患者样本中证实这些发现并确定具体的诱发病变。
Objective: To assess the role of hormone receptor/binding protein variants in genetic predisposition to premature ovarian failure (POF).Design: Case-control study.Setting: Academic.Patient(s): Fifty-five POF patients, 107 control women from the general population, and 27 control women who had proven fertility after age 37.Intervention(s): None.Main Outcome Measure(s): Allele distributions in cases and controls were assessed for genetic association.Result(s): Allele distributions of polymorphisms at the androgen receptor (AR) gene, estrogen receptor beta (ESR2) gene, sex hormone-binding globulin (SHBG) gene, and FSH receptor (FSHR) gene did not differ between patients and controls. At a repeat in a promoter of the estrogen receptor alpha (ESR1) gene, POF patients had fever (< 18) short repeat alleles than did controls (P = .004) vs. combined controls). Genotypes consisting of two short alleles were found in 36.4% of control women but only 5.5% of POF patients (P < .0001 vs. combined controls). The ESR1 repeat may confer risk for POF in a simple dominant manner in which carriers of a long repeat have a relative risk of 9.7 (95% CI = 2.6 - 35.6).Conclusion(s): Polymorphisms at the ESR1 gene are associated with POF in this patient population, while those in AR, ESR2, SHBG, and FSHR showed no association. Further studies are necessary to confirm these findings in larger patient samples and to identify the specific predisposing lesion.