Scripps VIVO scripps research logo

  • Index
  • Log in
  • Home
  • People
  • Organizations
  • Research
  • Events
Search form
As of April 1st VIVO Scientific Profiles will no longer updated for faculty, and the link to VIVO will be removed from the library website. Faculty profile pages will continue to be updated via Interfolio. VIVO will continue being used behind the scenes to update graduate student profiles. Please contact helplib@scripps.edu if you have questions.
How to download citations from VIVO | Alternative profile options

Toll-like receptor 4 polymorphisms are associated with resistance to Legionnaires' disease

Academic Article
uri icon
  • Overview
  • Research
  • Identity
  • Additional Document Info
  • View All
scroll to property group menus

Overview

authors

  • Hawn, T. R.
  • Verbon, A.
  • Janer, M.
  • Zhao, L. P.
  • Beutler, Bruce
  • Aderem, A.

publication date

  • February 2005

journal

  • Proceedings of the National Academy of Sciences of the United States of America  Journal

abstract

  • The immunogenetic factors that influence susceptibility to pneumonia are poorly understood. Recent studies suggest an association of toll-like receptor 4 (TLR4) polymorphisms with increased susceptibility to some infections. Here, we examined whether polymorphisms in TLR4 influence susceptibility to Legionnaires' disease (LD) by using a case-control study to compare the allele frequencies of two SNPs (A896G and C1196T). Cases (n = 108) were obtained from a LD outbreak in The Netherlands in 1999. Controls were exposed at the same outbreak, did not develop pneumonia, and were either unmatched (n = 421) or matched (n = 89) to patients for age, sex, and geographic residence. Allele 896G was associated with LD susceptibility with a frequency of 6.5% in the combined control group (matched and unmatched) vs. 2.5% in patients [odds ratio (OR) of 0.36, 95% confidence interval (C.I.) 0.14-0.91, P = 0.025]. In the matched control group comparison, allele 896G also showed a protective association with an OR of 0.27 (95% C.I. 0.09-0.75, P = 0.008). An analysis of genotype frequencies (896 AA vs. AG and GG) demonstrated similar protective associations (patient vs. combined control group comparison, OR = 0.35, 95% C.I. 0.14-0.89, P = 0.02; matched control group comparison, OR = 0.25, 95% C.I. 0.09-0.71, P = 0.006). Allele 1196T cosegregated with allele 896G and, thus, had identical associations. Although previous studies suggest that these TLR4 SNPs are associated with an increased risk of infection, this study demonstrates an association with resistance. This protective association illustrates that an innate immune receptor can mediate either beneficial or deleterious inflammatory responses and that these outcomes vary with different pathogens.

subject areas

  • Alleles
  • Case-Control Studies
  • Disease Outbreaks
  • Female
  • Gene Frequency
  • Genotype
  • Humans
  • Legionnaires' Disease
  • Male
  • Membrane Glycoproteins
  • Netherlands
  • Polymorphism, Single Nucleotide
  • Receptors, Cell Surface
  • Toll-Like Receptor 4
  • Toll-Like Receptors
scroll to property group menus

Research

keywords

  • genetic markers
  • immunity
  • inflammation
scroll to property group menus

Identity

PubMed Central ID

  • PMC549026

International Standard Serial Number (ISSN)

  • 0027-8424

Digital Object Identifier (DOI)

  • 10.1073/pnas.0409831102

PubMed ID

  • 15699327
scroll to property group menus

Additional Document Info

start page

  • 2487

end page

  • 2489

volume

  • 102

issue

  • 7

©2022 The Scripps Research Institute | Terms of Use | Powered by VIVO

  • About
  • Contact Us
  • Support