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

AI Article Synopsis

  • The review aimed to identify genetic variations linked to lower urinary tract symptoms and pelvic organ prolapse by analyzing various studies and assessing their reliability and biases.
  • Key findings included the rs4994 polymorphism of the ADRB3 gene showing a significant association with overactive bladder, while the rs1800012 polymorphism of the COL1A1 gene was linked with both prolapse and stress urinary incontinence.
  • Despite some associations being identified, the authors concluded that the evidence isn't strong enough to recommend clinical testing for these genetic polymorphisms.

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 In all, 27 published and 7 unpublished studies provided data on polymorphisms in or near 32 different genes.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

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4342521PMC
http://dx.doi.org/10.1016/j.ajog.2014.08.005DOI Listing

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