Systematic review and metaanalysis of genetic association studies of urinary symptoms and prolapse in women

Cartwright, Rufus and Kirby, Anna C. and Tikkinen, Kari A. O. and Mangera, Altaf and Thiagamoorthy, Gans and Rajan, Prabhakar and Pesonen, Jori and Ambrose, Chris and Gonzalez-Maffe, Juan and Bennett, Phillip and Palmer, Tom and Walley, Andrew and Järvelin, Marjo-Riitta and Chapple, Chris and Khullar, Vik (2015) Systematic review and metaanalysis of genetic association studies of urinary symptoms and prolapse in women. American Journal of Obstetrics and Gynecology, 212 (2). 199.e1-24. ISSN 0002-9378

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Abstract

OBJECTIVE: Family studies and twin studies demonstrate that lower urinary tract symptoms and pelvic organ prolapse are heritable. This review aimed to identify genetic polymorphisms tested for an association with lower urinary tract symptoms or prolapse, and to assess the strength, consistency, and risk of bias among reported associations. STUDY DESIGN: PubMed and HuGE Navigator were searched up to May 1, 2014, using a combination of genetic and phenotype key words, including "nocturia," "incontinence," "overactive bladder," "prolapse," and "enuresis." Major genetics, urology, and gynecology conference abstracts were searched from 2005 through 2013. We screened 889 abstracts, and retrieved 78 full texts. In all, 27 published and 7 unpublished studies provided data on polymorphisms in or near 32 different genes. Fixed and random effects metaanalyses were conducted using codominant models of inheritance. We assessed the credibility of pooled associations using the interim Venice criteria. RESULTS: In pooled analysis, the rs4994 polymorphism of the ADRB3 gene was associated with overactive bladder (odds ratio [OR], 2.5; 95% confidence interval [CI], 1.7-3.6; n = 419). The rs1800012 polymorphism of the COL1A1 gene was associated with prolapse (OR, 1.3; 95% CI, 1.0-1.7; n = 838) and stress urinary incontinence (OR, 2.1; 95% CI, 1.4-3.2; n = 190). Other metaanalyses, including those for polymorphisms of COL3A1,LAMC1,MMP1,MMP3, and MMP9 did not show significant effects. Many studies were at high risk of bias from genotyping error or population stratification. CONCLUSION: These metaanalyses provide moderate epidemiological credibility for associations of variation in ADRB3 with overactive bladder, and variation of COL1A1 with prolapse. Clinical testing for any of these polymorphisms cannot be recommended based on current evidence.

Item Type: Journal Article
Journal or Publication Title: American Journal of Obstetrics and Gynecology
Additional Information: Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.
Uncontrolled Keywords: /dk/atira/pure/subjectarea/asjc/2700/2729
Subjects:
Departments: Faculty of Science and Technology > Mathematics and Statistics
ID Code: 73934
Deposited By: ep_importer_pure
Deposited On: 18 Jun 2015 05:56
Refereed?: Yes
Published?: Published
Last Modified: 25 Feb 2020 07:23
URI: https://eprints.lancs.ac.uk/id/eprint/73934

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