A Systematic Review and In Silico Study of Potential Genetic Markers Implicated in Cases of Overactive Bladder

Major technology advances allowed us to study the expression of numerous genes simultaneously. Consequently, gene expression profiling will enable us to assess gene expression patterns and potentially identify many of them as prognostic markers. Identifying distinguishing genetic signatures can support patient risk stratification and treatment allocation. Our current study, titled “A Systematic Review of Potential Genetic Markers Affected in Overactive Bladder Cases and In Silico Study” which encloses available gene expression data, aims to facilitate the identification of a set of predictive biomarkers for overactive bladder (OAB) within the scope of this project.

In this study, we aimed to gather and synthesize available data from studies appraising differential gene expression in OAB patients compared to non-OAB controls and confine possible correlations and functional pathways between genes. 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/urine specimens alone. In addition, we employed several applications for in silico gene expression analysis alongside interactions data to validate the general significance of suggested markers.

The results of our systematic review have identified eleven genes as potential therapeutic targets being upregulated (P2RX2, SMTN, GAP43, TRPM8, CDH1, GJC1, CHRM2, CHRM3, TRPV4) or downregulated (P2RX3, P2RX5) in OAB patients. Genes were also found to be 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. Further analysis and validation are required for the gene markers, and interactions suggested in this study. Crosstalk between regulatory pathways and candidate gene factors is likely to define a landscape of OAB and should be considered for a personalized medicine approach. This systematic review provides an overview of gene expression changes in relation to OAB and therefore helps to formulate the actual knowledge gaps and research questions that need to be solved. In conclusion, a study of large databases of genetic information, coupled with translational advances, should permit selective investigations of predictive factors for more efficient application in female clinical urology.

Written by: Ilaha Isali, MD, Adonis Hijaz, MD, & David Sheyn, MD, University Hospitals Cleveland Medical Center, Case Western Reserve University, Cleveland, OH

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