Abstract
4 min readYou have accessJournal of UrologyBenign Prostatic Hyperplasia: Epidemiology & Natural History/Evaluation & Markers1 Apr 20131733 CANDIDATE GENE ASSOCIATION STUDIES OF LOWER URINARY TRACT SYMPTOMS IN MEN: A SYSTEMATIC REVIEW AND META-ANALYSIS Kari Tikkinen, Rufus Cartwright, Anna Kirby, Altaf Mangera, Gans Thiagamoorthy, Prabhakar Rajan, Jori Pesonen, Tom Palmer, Chris Ambrose, Vik Khullar, Andrew Walley, Marjo-Riitta Jarvelin, Phillip Bennett, and Chris Chapple Kari TikkinenKari Tikkinen Hamilton, Canada More articles by this author , Rufus CartwrightRufus Cartwright London, United Kingdom More articles by this author , Anna KirbyAnna Kirby San Diego, CA More articles by this author , Altaf MangeraAltaf Mangera Sheffield, 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 , Tom PalmerTom Palmer Bristol, United Kingdom More articles by this author , Chris AmbroseChris Ambrose London, United Kingdom More articles by this author , Vik KhullarVik Khullar London, United Kingdom More articles by this author , Andrew WalleyAndrew Walley 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 , and Chris ChappleChris Chapple Sheffield, United Kingdom More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2013.02.2903AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Lower urinary tract symptoms (LUTS) are heritable, with an affected relative conferring >1.5-fold increased risk, and twin studies indicating that genetic factors contribute at least half of phenotypic variation. We aimed to identify all candidate genes tested for an association with LUTS, and assess the strength, consistency, and risk of bias among reported associations. METHODS We systematically searched PubMed and HuGE Navigator through to October 2012 (all languages) using a combination of genetic and phenotype keywords and MeSH terms (including but not limited to LUTS, incontinence, nocturia, urgency and overactive bladder). In addition we searched AUA, EAU, and ICS meeting abstracts 2005-2011. We hand searched reference lists of included articles and contacted study authors for clarifications. We included only case control studies that either used LUTS for the case definition, or recruited participants receiving treatment for LUTS. 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). We assessed the credibility of pooled associations using the interim Venice criteria[1]. RESULTS We screened 1025 abstracts, and retrieved 188 full texts. 54 studies provided usable data on polymorphisms in or near 44 different genes. All included studies tested associations with composite definitions of symptomatic BPH. For the most studied variant, the CAG(n) repeat in the androgen receptor (AR), there was no overall association with mean copy number (see table). Pooled analyses suggested significant effects for polymorphisms of cytochrome P450-17 (CYP17), glutathione S-transferase-M1 (GSTM1), interleukin 4 (IL4), steroid 5-alpha-reductase (SRD5A2), and the vitamin D receptor (VDR). Many studies were at risk of bias from genotyping error or selective outcome reporting. CONCLUSIONS These meta-analyses provide moderate epidemiological credibility[1] for association of variation in or near CYP17, GSTM1, IL4, SRD5A2 and VDR with LUTS. Since the etiologies of storage and voiding symptoms may be entirely disparate, further advances will require focus on individual symptoms, likely within the context of larger genome-wide association studies. 1. Int J Epidemiol. 2008;37(1):120-32 Gene Polymorphism n studies n participants Pooled OR 95%CI ACE rs4646994 2 355 3.31 0.40-27.06 AR CAG(n) >21 / <=21 4 2675 0.7 0.67-0.94 AR CAG(n) / copy 5 1432 0.02 -0.1-0.14 CYP17 rs743572 2 789 1.39 1.14-1.71 FGFR4 rs2011077 2 783 0.92 0.74-1.15 GSTM1 null 4 1128 0.53 0.42-0.68 GSTT1 null 4 1162 0.87 0.64-1.18 GSTP1 rs1696 2 501 1.08 0.80-1.46 IFNG rs2430561 2 618 1.13 0.90-1.43 IGFBP3 rs2854744 2 1165 0.88 0.74-1.04 IL1RN intron 2 VNTR 2 700 0.92 0.73-1.16 IL4 intron 3 VNTR 2 707 0.69 0.53-0.90 IL10 rs1800896 2 613 0.92 0.72-1.10 PSA rs266882 2 720 0.85 0.47-1.51 SRD5A2 rs523349 3 913 1.06 0.86-1.28 SRD5A2 rs9282858 2 443 0.33 0.14-0.80 TGFB1 rs1800470 4 1449 0.99 0.85-1.15 TNF rs1800629 2 619 0.94 0.69-1.28 VDR rs731236 5 1053 0.64 0.52-0.79 VDR rs1544410 3 731 0.78 0.62-0.98 VDR rs17879735 2 411 1.10 0.81-1.48 VDR rs10735810 2 1011 1.11 0.91-1.36 © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 189Issue 4SApril 2013Page: e712 Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.MetricsAuthor Information Kari Tikkinen Hamilton, Canada More articles by this author Rufus Cartwright London, United Kingdom More articles by this author Anna Kirby San Diego, CA More articles by this author Altaf Mangera Sheffield, 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 Tom Palmer Bristol, United Kingdom More articles by this author Chris Ambrose London, United Kingdom More articles by this author Vik Khullar London, United Kingdom More articles by this author Andrew Walley 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 Expand All Advertisement Advertisement PDF downloadLoading ...
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