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

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.