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Recurrent urinary tract infection genetic risk: a systematic review and gene network analysis

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Abstract

Introduction and hypothesis

The development of recurrent urinary tract infections (rUTIs) is not completely understood. This review is aimed at investigating the connection between genetics and rUTIs and summarizing the results of studies that have documented variations in gene expression among individuals with rUTIs compared with healthy individuals.

Methods

A systematic search was conducted in Cochrane, Ovid, and PubMed, limiting the results to articles published between 1 January 2000, and 5 July 2022. Only studies comparing the difference in gene expression between individuals with rUTI and healthy individuals utilizing molecular techniques to measure gene expression in blood or urine samples were included in this systematic review. Gene network and pathways analyses were performed using Cytoscape software, with input data obtained from our systematic review of differentially expressed genes in rUTIs.

Results

Six studies met our criteria for inclusion. The selected studies used molecular biology methods to quantify gene expression data from blood specimens. The analysis revealed that gene expressions of CXCR1 and TLR4 decreased, whereas CXCR2, TRIF, and SIGIRR increased in patients with rUTI compared with healthy controls. The analysis demonstrated that the most significant pathways were associated with TLR receptor signaling and tolerance, I-kappa B kinase/NF-kappa B signaling, and MyD88-independent TLR signaling.

Conclusions

This systematic review uncovered gene expression variations in several candidate genes and identified a number of underlying biological pathways associated with rUTIs. These findings could shift the treatment and prevention strategies for rUTIs.

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Authors and Affiliations

  1. Department of Urology, University Hospitals, Cleveland Medical Center, Cleveland, OH, USA

    Ilaha Isali, Thomas R. Wong, Ali Furkan Batur, Chen-Han Wilfred Wu, Rachel Pope, Adonis Hijaz & David Sheyn

  2. Department of Genetics and Genome Sciences, Case Western Reserve University School of Medicine, Cleveland, OH, USA

    Chen-Han Wilfred Wu

  3. Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, OH, USA

    Fredrick R. Schumacher

  4. Department of Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, OH, USA

    Fredrick R. Schumacher

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  1. Ilaha Isali
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Contributions

I.I.: manuscript writing, project development, analysis; T.R.W.: manuscript writing, abstract/paper review/analysis; A.F.B.: manuscript writing, abstract/paper review; C.H.W.W.: analysis, manuscript writing; F.R.S.: manuscript writing, analysis; R.P.: manuscript writing; A.H.: manuscript writing; D.S.: project development, manuscript writing, project oversight.

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Correspondence to David Sheyn.

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Conflicts of interest

D.S.: Renalis (research support), Caldera (consulting fee); A.H.: Collamedix (ownership stake); R.P.: Johnson & Johnson, MaternaMD (consulting fee), ; none of the other authors report any conflicts of interest.

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Isali, I., Wong, T.R., Batur, A.F. et al. Recurrent urinary tract infection genetic risk: a systematic review and gene network analysis. Int Urogynecol J 35, 259–271 (2024). https://doi.org/10.1007/s00192-023-05671-6

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  • DOI: https://doi.org/10.1007/s00192-023-05671-6

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