A systematic review of underlying genetic factors associated with ureteropelvic junction obstruction in stenotic human tissue

Objective: Genetic factors are implicated in the development of ureteropelvic junction obstruction (UPJO). The aims of this study were: 1) condense and examine the existing data in studies containing information regarding differential gene expression in tissues from patients with UPJO and 2) investigate associations between genetic markers and their related pathways.

Materials and methods: A systematic review of studies published between January 2000 and September 2021 was conducted using the following databases: Ovid/Medline, PubMed, Wiley Cochrane Central Register of Controlled Trials, Web of Science, and Scopus. Of 249 studies, 10 were included in the final analysis. The search was performed using the terms "ureteropelvic junction obstruction", "genetic", "gene", and "gene expression". Literature pertaining to differential gene expression in UPJO patients as compared to healthy controls was identified. Studies containing gene expression and quantification of molecular data carried out directly on stenotic tissue samples were selected for analysis. Gene network connections and functional analyses were then determined using MetaScape software.

Results: From the ten studies identified for analysis, fifteen genes were noted as differentially expressed. In UPJO patients, nine genes were upregulated (ET1, ACTA2, MCP-1, TGFB1, NFKB1, IL-6, HIF1A, S100A1, SYP) and six were downregulated (ADM, NOS2, EGF, PDGFRA, UCHL1, NGFR). These genes were principally involved in HIF-1 signaling pathway, blood vessel development, positive regulation of signaling receptor activity, and Ras signaling pathway.

Conclusions: A potential link exists between genes related to hypoxia, excessive fibrous tissue formation, and inflammation in the development of UPJO, and these connections merit more detailed, tissue level investigations in UPJO patients. The outcomes of this systematic review may lay the groundwork for the development of future targeted therapies and novel biomarker detection for treatments, early detection, and possible prediction and prevention of development of UPJO.