Genetic polymorphisms associated with urinary tract infection in children and adults: a systematic review and meta-analysis

• Published in: American journal of obstetrics and gynecology Vol. 230; no. 6; pp. 600 - 609.e3
• Main Authors: Yu, Jiakun, Varella Pereira, Glaucia Miranda, Allen-Brady, Kristina, Cuffolo, Romana, Siddharth, Aditi, Koch, Marianne, Chua, John W.F., Sorrentino, Felice, Dytko, Oskar, Ng, Kaa-Yung, Violette, Philippe, Khullar, Vik, Wang, Zhan Tao, Cartwright, Rufus
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.06.2024
• Subjects: Adult; Child; genetic association; genetic polymorphism; Genetic Predisposition to Disease; Genome-Wide Association Study; Humans; Polymorphism, Genetic; Polymorphism, Single Nucleotide; single nucleotide polymorphism; urinary tract infection; Urinary Tract Infections - genetics; genetic association; single nucleotide polymorphism; genetic polymorphism; urinary tract infection
• ISSN: 0002-9378; 1097-6868; 1097-6868
• DOI: 10.1016/j.ajog.2023.12.018

The lifetime risk of urinary tract infection is known from first-degree relative studies to be highly heritable. Associations have also been observed across the life course from pediatric urinary tract infection to recurrent urinary tract infection in adulthood, suggesting lifelong susceptibility factors. Candidate gene studies and genome-wide association studies have tested for genetic associations of urinary tract infection; however, no contemporary systematic synthesis of studies is available. We conducted a systematic review to identify all genetic polymorphisms tested for an association with urinary tract infection in children and adults; and to assess their strength, consistency, and risk of bias among reported associations. PubMed, HuGE Navigator and Embase were searched from January 1, 2005 to November 16, 2023, using a combination of genetic and phenotype key words. Fixed and random effects meta-analyses were conducted using codominant models of inheritance in metan. The interim Venice criteria were used to assess their credibility of pooled associations. After removing 451 duplicates, 1821 studies reports were screened, with 106 selected for full-text review, 22 were included in the meta-analysis (7 adult studies and 15 pediatric studies). Our meta-analyses demonstrated significant pooled associations for pediatric urinary tract infection with variation in CXCR1, IL8, TGF, TLR4 and VDR; all of which have plausible roles in the pathogenesis of urinary tract infection. Our meta-analyses also demonstrated a significant pooled association for adult urinary tract infection with variation in CXCR1. All significant pooled associations were graded according to their epidemiological credibility, sample sizes, heterogeneity between studies, and risk of bias. This systematic review provides a current synthesis of the known genetic architecture of urinary tract infection in childhood and adulthood; and should provide important information for researchers analysing future genetic association studies. Although, overall, the credibility of pooled associations was weak, the consistency of findings for rs2234671 single nucleotide polymorphisms of CXCR1 in both populations suggest a key role in the urinary tract infection pathogenesis.