116 CANDIDATE GENE ASSOCIATION STUDIES OF URINARY SYMPTOMS AND PELVIC ORGAN PROLAPSE IN WOMEN: A SYSTEMATIC REVIEW AND META-ANALYSIS

You have accessJournal of UrologyUrodynamics/Incontinence/Female Urology: Basic Research (II)1 Apr 2013116 CANDIDATE GENE ASSOCIATION STUDIES OF URINARY SYMPTOMS AND PELVIC ORGAN PROLAPSE IN WOMEN: A SYSTEMATIC REVIEW AND META-ANALYSIS Anna Kirby, Rufus Cartwright, Kari Tikkinen, Tom Palmer, Gans Thiagamoorthy, Prabhakar Rajan, Jori Pesonen, Andrew Walley, Altaf Mangera, Georgios Grigoriadis, Chris Ambrose, Marjo-Riitta Jarvelin, Phillip Bennett, Chris Chapple, and Vik Khullar Anna KirbyAnna Kirby San Diego, CA More articles by this author , Rufus CartwrightRufus Cartwright London, United Kingdom More articles by this author , Kari TikkinenKari Tikkinen Hamilton, Canada More articles by this author , Tom PalmerTom Palmer Bristol, United Kingdom More articles by this author , Gans ThiagamoorthyGans Thiagamoorthy London, United Kingdom More articles by this author , Prabhakar RajanPrabhakar Rajan Glasgow, United Kingdom More articles by this author , Jori PesonenJori Pesonen Tampere, Finland More articles by this author , Andrew WalleyAndrew Walley London, United Kingdom More articles by this author , Altaf MangeraAltaf Mangera Sheffield, United Kingdom More articles by this author , Georgios GrigoriadisGeorgios Grigoriadis London, United Kingdom More articles by this author , Chris AmbroseChris Ambrose London, United Kingdom More articles by this author , Marjo-Riitta JarvelinMarjo-Riitta Jarvelin London, United Kingdom More articles by this author , Phillip BennettPhillip Bennett London, United Kingdom More articles by this author , Chris ChappleChris Chapple Sheffield, United Kingdom More articles by this author , and Vik KhullarVik Khullar London, United Kingdom More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2013.02.1495AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Family and classical twin studies have suggested that urgency and stress urinary incontinence (UUI and SUI), as well as pelvic organ prolapse (POP) are heritable, with an affected first degree relative conferring >2 fold risk, and genetic factors contributing half of liability. We aimed to identify all candidate genes tested for an association with POP or LUTS, and assess the strength, consistency, and risk of bias among associations. METHODS We searched PubMed and HuGE Navigator through to October 2012 (all languages) using a combination of genetic and phenotype keywords and MeSH terms (including nocturia, LUTS, incontinence, urgency, overactive bladder (OAB), and prolapse). In addition we searched AUA, EAU, IUGA, and ICS meeting abstracts 2005-2011. We hand searched reference lists of included articles, and contacted study authors for clarifications. We performed all screening and data extraction in duplicate. For polymorphisms assessed in >=2 studies for the same phenotype, we conducted fixed and random effects meta-analyses using the Metan package (Stata 12.1), using codominant models of inheritance. We assessed the credibility of pooled associations using the interim Venice criteria[1]. RESULTS We screened 1025 abstracts, and retrieved 188 full texts. 26 published and 8 unpublished studies provided usable data on polymorphisms of 19 different genes, in association with SUI, OAB or POP. In pooled analyses (see table), a common polymorphism of the beta 3 adrenoceptor (ADRB3) was associated with increased risk of OAB, while a polymorphism of collagen type 1 alpha 1 (COL1A1) showed significant associations with both SUI and POP, and a further polymorphism of collagen type 3 alpha 1 (COL3A1) was associated with POP. In other meta-analyses for polymorphisms of LAMC1, MMP1, MMP3 and MMP9 there was no significant effect. Many studies were at risk of bias from either genotyping error or population stratification. CONCLUSIONS These meta-analyses provide moderate epidemiological credibility[1] for associations of variation in 1) ADRB3 with OAB, 2) COL1A1 with SUI and POP, and 3) COL3A1 with POP. Such variation accounts for a small proportion of the observed heritability, and further discoveries may require larger genome-wide studies. 1. Int J Epidemiol. 2008;37(1):120-32 Gene Polymorphism Phenotype n studies n participants Pooled OR 95%CI ADRB3 rs4994 OAB 2 419 2.46 1.67-3.60 COL1A1 rs1800012 SUI 2 190 2.09 1.35-3.22 COL1A1 rs1800012 POP 4 838 1.33 1.02-1.73 COL3A1 rs1800255 POP 2 537 1.36 1.01-1.82 COL3A1 rs111929073 POP 2 385 0.56 0.19-1.61 LAMC1 rs10911193 POP 3 844 1.12 0.83-2.01 LAMC1 rs20563 POP 2 780 1.12 0.92-1.39 LAMC1 rs20558 POP 2 789 1.12 0.92-1.38 MMP1 rs1799750 POP 2 499 0.84 0.65-1.08 MMP3 rs3025028 POP 2 491 1.11 0.86-1.43 MMP9 rs3918242 POP 2 477 1.25 0.83-1.89 MMP9 rs17576 POP 3 710 0.98 0.78-1.24 © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 189Issue 4SApril 2013Page: e47 Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.Metrics Author Information Anna Kirby San Diego, CA More articles by this author Rufus Cartwright London, United Kingdom More articles by this author Kari Tikkinen Hamilton, Canada More articles by this author Tom Palmer Bristol, United Kingdom More articles by this author Gans Thiagamoorthy London, United Kingdom More articles by this author Prabhakar Rajan Glasgow, United Kingdom More articles by this author Jori Pesonen Tampere, Finland More articles by this author Andrew Walley London, United Kingdom More articles by this author Altaf Mangera Sheffield, United Kingdom More articles by this author Georgios Grigoriadis London, United Kingdom More articles by this author Chris Ambrose London, United Kingdom More articles by this author Marjo-Riitta Jarvelin London, United Kingdom More articles by this author Phillip Bennett London, United Kingdom More articles by this author Chris Chapple Sheffield, United Kingdom More articles by this author Vik Khullar London, United Kingdom More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...