Toll-like Receptor Polymorphisms and Susceptibility to Urinary Tract Infections in Adult Women

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2009 Jun 23

PMID 19543401

Citations 94

Authors

Thomas R Hawn

Delia Scholes

Shuying S Li

Hongwei Wang

Yin Yang

Pacita L Roberts

Ann E Stapleton

Marta Janer

Alan Aderem

Walter E Stamm

Lue Ping Zhao

Thomas M Hooton

Affiliations

Soon will be listed here.

Abstract

Background: Although behavioral risk factors are strongly associated with urinary tract infection (UTI) risk, the role of genetics in acquiring this disease is poorly understood.

Methodology/principal Findings: To test the hypothesis that polymorphisms in Toll-like receptor (TLR) pathway genes are associated with susceptibility to UTIs, we conducted a population-based case-control study of women ages 18-49 years. We examined DNA variants in 9 TLR pathway genes in 431 recurrent cystitis (rUTI) cases, 400 pyelonephritis cases, and 430 controls with no history of UTIs. In the Caucasian subgroup of 987 women, polymorphism TLR4_A896G was associated with protection from rUTI, but not pyelonephritis, with an odds ratio (OR) of 0.54 and a 95% confidence interval (CI) of 0.31 to 0.96. Polymorphism TLR5_C1174T, which encodes a variant that abrogates flagellin-induced signaling, was associated with an increased risk of rUTI (OR(95%CI): 1.81 (1.00-3.08)), but not pyelonephritis. Polymorphism TLR1_G1805T was associated with protection from pyelonephritis (OR(95%CI): 0.53 (0.29-0.96)).

Conclusions: These results provide the first evidence of associations of TLR5 and TLR1 variants with altered risks of acquiring rUTI and pyelonephritis, respectively. Although these data suggest that TLR polymorphisms are associated with adult susceptibility to UTIs, the statistical significance was modest and will require further study including validation with independent cohorts.

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