deCODE Genetics/Amgen, Sturlugata 8, 101, Reykjavik, Iceland.
Department of Obstetrics and Gynecology, Landspitali University Hospital, 101, Reykjavik, Iceland.
Commun Biol. 2020 Mar 17;3(1):129. doi: 10.1038/s42003-020-0857-9.
Pelvic organ prolapse (POP) is a downward descent of one or more of the pelvic organs, resulting in a protrusion of the vaginal wall and/or uterus. We performed a genome-wide association study of POP using data from Iceland and the UK Biobank, a total of 15,010 cases with hospital-based diagnosis code and 340,734 female controls, and found eight sequence variants at seven loci associating with POP (P < 5 × 10); seven common (minor allele frequency >5%) and one with minor allele frequency of 4.87%. Some of the variants associating with POP also associated with traits of similar pathophysiology. Of these, rs3820282, which may alter the estrogen-based regulation of WNT4, also associates with leiomyoma of uterus, gestational duration and endometriosis. Rs3791675 at EFEMP1, a gene involved in connective tissue homeostasis, also associates with hernias and carpal tunnel syndrome. Our results highlight the role of connective tissue metabolism and estrogen exposure in the etiology of POP.
盆腔器官脱垂（POP）是指一个或多个盆腔器官向下移位，导致阴道壁和/或子宫突出。我们使用冰岛和英国生物银行的数据对 POP 进行了全基因组关联研究，共纳入 15010 例基于医院诊断代码的病例和 340734 名女性对照，在 7 个位点发现了 8 个与 POP 相关的序列变异（P<5×10-8）；其中 7 个为常见变异（次要等位基因频率>5%），1 个为罕见变异（次要等位基因频率为 4.87%）。与 POP 相关的一些变异也与具有相似病理生理学特征的性状相关。其中，rs3820282 可能改变了 WNT4 的雌激素基础调控，也与子宫肌瘤、妊娠持续时间和子宫内膜异位症相关。EFEMP1 上的 rs3791675 与连接组织稳态有关，也与疝和腕管综合征相关。我们的研究结果强调了结缔组织代谢和雌激素暴露在 POP 发病机制中的作用。
