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

Rufus Cartwright*, Anna C. Kirby, Kari A.O. Tikkinen, Altaf Mangera, Gans Thiagamoorthy, Prabhakar Rajan, Jori Pesonen, Chris Ambrose, Juan Gonzalez-Maffe, Phillip Bennett, Tom Palmer, Andrew Walley, Marjo Riitta Järvelin, Chris Chapple, Vik Khullar

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

83 Citations (Scopus)


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 In all, 27 published and 7 unpublished studies provided data on polymorphisms in or near 32 different genes.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.

Original languageEnglish
Pages (from-to)199.e1-199.e24
JournalAmerican Journal of Obstetrics and Gynecology
Issue number2
Publication statusPublished - 1 Feb 2015


  • genetics
  • incontinence
  • lower urinary tract symptoms
  • overactive bladder
  • prolapse
  • systematic review


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