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A systematic review and in silico study of potential genetic markers implicated in cases of overactive bladder - 22/12/22

Doi : 10.1016/j.ajog.2022.07.044 
Ilaha Isali, MD a, Phillip McClellan, PhD a, Thomas R. Wong a, Clara Sun, BS a, Amber Catherine Stout, MLIS, MLitt b, Fredrick R. Schumacher, PhD c, Sarah Markt, ScD c, Chen-Han Wilfred Wu, MD, PhD a, d, Kathryn L. Penney, ScD e, f, Sherif El-Nashar, MD, PhD g, Adonis Hijaz, MD a, David Sheyn, MD a,
a Division of Female Pelvic Medicine and Reconstructive Surgery, Department of Urology, University Hospitals, Cleveland Medical Center, Cleveland, OH 
b Core library, University Hospitals, Cleveland Medical Center, Cleveland, OH 
c Department of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, OH 
d Department of Genetics and Genome Sciences, Case Western Reserve University, Cleveland, OH 
e Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA 
f Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 
g Department of Obstetrics and Gynecology, Mayo Clinic, Jacksonville, FL 

Corresponding author: David Sheyn, MD.

Abstract

Objective

The contribution of genetic factors to the presence of an overactive bladder is recognized. This study aimed to (1) assemble and synthesize available data from studies assessing differential gene expression in patients with overactive bladder vs controls without overactive bladder and (2) determine possible correlations and functional pathways between genes.

Data Sources

We searched PubMed, Ovid or Medline, and Wiley Cochrane Central Register of Controlled Trials databases between January 1, 2000, and December 15, 2021.

Study Eligibility Criteria

Studies were included if gene expression was detected and quantified using molecular approaches performed on human bladder tissue specimens directly and excluded if the gene expression analysis was carried out from blood and urine specimens alone.

Methods

A systematic review was completed to identify publications that reported differently expressed gene candidates among patients with overactive bladder vs healthy individuals. Gene networking connections and pathway analysis were performed employing Metascape software, where inputs were identified from our systematic review of differentially expressed genes in overactive bladder.

Results

A total of 9 studies were included in the final analysis and 11 genes were identified as being up-regulated (purinergic receptor P2X 2 [P2RX2], smoothelin [SMTN], growth-associated protein 43 [GAP43], transient receptor potential cation channel subfamily M member 8 [TRPM8], cadherin 11 [CDH1], gap junction protein gamma 1 [GJC1], cholinergic receptor muscarinic 2 [CHRM2], cholinergic receptor muscarinic 3 [CHRM3], and transient receptor potential cation channel subfamily V member 4 [TRPV4]) or down-regulated (purinergic receptor P2X 2 [P2RX3] and purinergic receptor P2X 5 [P2RX5]) in patients with overactive bladder. Gene network analysis showed that genes are involved in chemical synaptic transmission, smooth muscle contraction, blood circulation, and response to temperature stimulus. Network analysis demonstrated a significant genetic interaction between TRPV4, TRPM8, P2RX3, and PR2X2 genes.

Conclusion

Outcomes of this systematic review highlighted potential biomarkers for treatment efficacy and have laid the groundwork for developing future gene therapies for overactive bladder in clinical settings.

Le texte complet de cet article est disponible en PDF.

Key words : gene expression, genomics, overactive bladder, systematic review, urge urinary incontinence


Plan


 The authors report no conflict of interest.
 This study received no financial support.
 This study was registered in the Open Science Framework (knfud) on July 1, 2020.


© 2022  Elsevier Inc. Tous droits réservés.
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Vol 228 - N° 1

P. 36 - janvier 2023 Retour au numéro
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