Department of Internal Medicine, Genetic Epidemiology, University of Utah, Salt Lake City, UT, USA.
Zhongshan Hospital, Fudan University, Shanghai, China.
Int Urogynecol J. 2022 Jan;33(1):67-82. doi: 10.1007/s00192-021-04782-2. Epub 2021 Apr 24.
Family and twin studies demonstrate that pelvic organ prolapse (POP) is heritable, but the genetic etiology is poorly understood. This review aimed to identify genetic loci and specific polymorphisms associated with POP, while assessing the strength, consistency, and risk of bias among reported associations.
Updating an earlier systematic review, PubMed and HuGE Navigator as well as relevant conference abstracts were searched using genetic and phenotype keywords from 2015 to 2020. Screening and data extraction were performed in duplicate. Fixed and random effects meta-analyses were conducted using co-dominant models of inheritance. We assessed credibility of pooled associations using interim Venice criteria.
We screened 504 new abstracts and included 46 published and 7 unpublished studies. In pooled analyses we found significant associations for four polymorphisms: rs2228480 at the ESR1 gene (OR 0.67 95% CI 0.46-0.98, I = 0.0%, Venice rating BAB), rs12589592 at the FBLN5 gene (OR 1.46 95% CI 1.11-1.82, I = 36.3%, Venice rating BBB), rs484389 in the PGR gene (OR 0.61 95% CI 0.39-0.96, I = 32.4%, Venice rating CBB), and rs1800012 at the COL1A1 gene (OR 0.80 95% CI 0.66-0.96, I = 0.0%, Venice rating BAB). Further credible novel variants have also been recently identified in genome-wide association studies.
The genetic contributions to POP remain poorly understood. Several biologically plausible variants have been identified, but much work is required to establish the role of these genes in the pathogenesis of POP or to establish a role for genetic testing in clinical practice.
家庭和双胞胎研究表明，盆腔器官脱垂（POP）是可遗传的，但遗传病因尚不清楚。本综述旨在确定与 POP 相关的遗传位点和特定多态性，并评估报告相关性的强度、一致性和偏倚风险。
更新之前的系统综述，使用遗传和表型关键词，从 2015 年到 2020 年在 PubMed 和 HuGE Navigator 以及相关会议摘要中进行搜索。筛查和数据提取由两人进行。使用遗传模型进行固定和随机效应荟萃分析。我们使用临时威尼斯标准评估汇总关联的可信度。
我们筛选了 504 篇新摘要，纳入了 46 篇已发表和 7 篇未发表的研究。在汇总分析中，我们发现四个多态性存在显著相关性：ESR1 基因的 rs2228480（OR 0.67，95%CI 0.46-0.98，I=0.0%，威尼斯评级 BAB）、FBLN5 基因的 rs12589592（OR 1.46，95%CI 1.11-1.82，I=36.3%，威尼斯评级 BBB）、PGR 基因的 rs484389（OR 0.61，95%CI 0.39-0.96，I=32.4%，威尼斯评级 CBB）和 COL1A1 基因的 rs1800012（OR 0.80，95%CI 0.66-0.96，I=0.0%，威尼斯评级 BAB）。最近在全基因组关联研究中也发现了一些可信的新变体。
遗传因素对 POP 的影响仍知之甚少。已经确定了一些具有生物学意义的变体，但还需要做大量工作来确定这些基因在 POP 发病机制中的作用，或者在临床实践中建立基因检测的作用。
