Toll-like receptor polymorphisms and susceptibility to urinary tract infections in adult women

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 Hooton

Research output: Contribution to journalArticle

129 Citations (Scopus)

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.

Original languageEnglish
Article numbere5990
JournalPLoS One
Volume4
Issue number6
DOIs
StatePublished - Jun 22 2009

Fingerprint

pyelonephritis
urinary tract diseases
Toll-Like Receptors
Pyelonephritis
cystitis
Polymorphism
Urinary Tract Infections
Cystitis
genetic polymorphism
odds ratio
confidence interval
Odds Ratio
Confidence Intervals
Genes
Toll-Like Receptor 9
Flagellin
flagellin
Validation Studies
genetic disorders
case-control studies

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Toll-like receptor polymorphisms and susceptibility to urinary tract infections in adult women. / Hawn, Thomas R.; Scholes, Delia; Li, Shuying S.; Wang, Hongwei; Yang, Yin; Roberts, Pacita L.; Stapleton, Ann E.; Janer, Marta; Aderem, Alan; Stamm, Walter E.; Zhao, Lue Ping; Hooton, Thomas.

In: PLoS One, Vol. 4, No. 6, e5990, 22.06.2009.

Research output: Contribution to journalArticle

Hawn, TR, Scholes, D, Li, SS, Wang, H, Yang, Y, Roberts, PL, Stapleton, AE, Janer, M, Aderem, A, Stamm, WE, Zhao, LP & Hooton, T 2009, 'Toll-like receptor polymorphisms and susceptibility to urinary tract infections in adult women', PLoS One, vol. 4, no. 6, e5990. https://doi.org/10.1371/journal.pone.0005990
Hawn, Thomas R. ; Scholes, Delia ; Li, Shuying S. ; Wang, Hongwei ; Yang, Yin ; Roberts, Pacita L. ; Stapleton, Ann E. ; Janer, Marta ; Aderem, Alan ; Stamm, Walter E. ; Zhao, Lue Ping ; Hooton, Thomas. / Toll-like receptor polymorphisms and susceptibility to urinary tract infections in adult women. In: PLoS One. 2009 ; Vol. 4, No. 6.
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AU - Janer, Marta

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AU - Hooton, Thomas

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AB - 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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