Research output: Contribution to Journal/Magazine › Journal article › peer-review
Research output: Contribution to Journal/Magazine › Journal article › peer-review
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TY - JOUR
T1 - Systematic review and metaanalysis of genetic association studies of urinary symptoms and prolapse in women
AU - Cartwright, Rufus
AU - Kirby, Anna C.
AU - Tikkinen, Kari A. O.
AU - Mangera, Altaf
AU - Thiagamoorthy, Gans
AU - Rajan, Prabhakar
AU - Pesonen, Jori
AU - Ambrose, Chris
AU - Gonzalez-Maffe, Juan
AU - Bennett, Phillip
AU - Palmer, Tom
AU - Walley, Andrew
AU - Järvelin, Marjo-Riitta
AU - Chapple, Chris
AU - Khullar, Vik
N1 - Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.
PY - 2015/2
Y1 - 2015/2
N2 - 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 In all, 27 published and 7 unpublished studies provided data on polymorphisms in or near 32 different genes.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.
AB - 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.
KW - Female
KW - Genetic Association Studies
KW - Genotype
KW - Humans
KW - Lower Urinary Tract Symptoms
KW - Odds Ratio
KW - Pelvic Organ Prolapse
U2 - 10.1016/j.ajog.2014.08.005
DO - 10.1016/j.ajog.2014.08.005
M3 - Journal article
C2 - 25111588
VL - 212
SP - 199.e1-24
JO - American Journal of Obstetrics and Gynecology
JF - American Journal of Obstetrics and Gynecology
SN - 0002-9378
IS - 2
ER -