Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Meta-Analysis
. 2022 Jan;33(1):67-82.
doi: 10.1007/s00192-021-04782-2. Epub 2021 Apr 24.

Systematic review and meta-analysis of genetic association studies of pelvic organ prolapse

Kristina Allen-Brady  1 , John W F Chua  2 , Romana Cuffolo  3 , Marianne Koch  4 , Felice Sorrentino  5 , Rufus Cartwright  6   7
Affiliations
Meta-Analysis

Systematic review and meta-analysis of genetic association studies of pelvic organ prolapse

Kristina Allen-Brady et al. Int Urogynecol J. 2022 Jan.

Abstract

Introduction and hypothesis: 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.

Methods: 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.

Results: We screened 504 new abstracts and included 46 published and 7 unpublished studies.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, I2 = 0.0%, Venice rating BAB), rs12589592 at the FBLN5 gene (OR 1.46 95% CI 1.11-1.82, I2 = 36.3%, Venice rating BBB), rs484389 in the PGR gene (OR 0.61 95% CI 0.39-0.96, I2 = 32.4%, Venice rating CBB), and rs1800012 at the COL1A1 gene (OR 0.80 95% CI 0.66-0.96, I2 = 0.0%, Venice rating BAB). Further credible novel variants have also been recently identified in genome-wide association studies.

Conclusion: 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.

Keywords: Genetics; Meta-analysis; Prolapse.

PubMed Disclaimer

Conflict of interest statement

None.

Figures

Fig. 1
Fig. 1
Flowchart outlining the literature search and article evaluation process. a ASHG, ESHG, ICS, IUGA, AUA, SGS, AUGS, and EAU abstracts 2005–2020 using search interfaces at http://www.ics.org/publications/abstracts, http://www.sciencedirect.com/science/journal/15699056, http://www.jurology.com/supplements, http://www.ashg.org/meetings/meetings_abstract_search.shtml, and/or full text search of abstract book PDFs. b Includes reviews (n = 2), inapplicable phenotypes (n = 3), and other study designs including pharmacogenetic studies, gene expression studies, or methylation studies (n = 33)
Fig. 2
Fig. 2
Forest plot of meta-analysis of studies of the rs2228480 SNP in the gene ESR1
Fig. 3
Fig. 3
Forest plot of meta-analysis of studies of the rs12589592 SNP in the gene FBLN5
Fig. 4
Fig. 4
Forest plot of meta-analysis of studies of the rs484389 SNP in the gene PGR
Fig. 5
Fig. 5
Forest plot of meta-analysis of studies of the rs1800012 SNP in the gene COL1A1
See this image and copyright information in PMC

Comment in

References

    1. Thompson H. On irritability of the bladder. Lancet. 1854;63:637–638. doi: 10.1016/S0140-6736(02)40600-9. - DOI
    1. Friedman T, Eslick GD, Dietz HP. Risk factors for prolapse recurrence: systematic review and meta-analysis. Int Urogynecol J. 2018;29(1):13–21. doi: 10.1007/s00192-017-3475-4. - DOI - PubMed
    1. Lince SL, van Kempen LC, Vierhout ME, Kluivers KB. A systematic review of clinical studies on hereditary factors in pelvic organ prolapse. Int Urogynecol J. 2012;23(10):1327–1336. doi: 10.1007/s00192-012-1704-4. - DOI - PMC - PubMed
    1. Samimi P, Jones SH, Giri A. Family history and pelvic organ prolapse: a systematic review and meta-analysis. Int Urogynecol J. ePublication ahead of print. 2020. 10.1007/s00192-020-04559-z. - PMC - PubMed
    1. Hamer MA, Persson J. Familial predisposition to pelvic floor dysfunction: prolapse and incontinence surgery among family members and its relationship with age or parity in a Swedish population. Eur J Obstet Gynecol Reprod Biol. 2013;170(2):559–562. doi: 10.1016/j.ejogrb.2013.07.025. - DOI - PubMed