Polymorphisms in toll-like receptor 4 are not associated with asthma or atopy-related phenotypes

Benjamin A. Raby, Walter T. Klimecki, Catherine Laprise, Yannick Renaud, Janet Faith, Mathieu Lemire, Celia Greenwood, Katherine M. Weiland, Christoph Lange, Lyle J. Palmer, Ross Lazarus, Donata Vercelli, David J. Kwiatkowski, Edwin K. Silverman, Fernando D. Martinez, Thomas J. Hudson, Scott T. Weiss

Research output: Contribution to journalArticlepeer-review

147 Scopus citations

Abstract

Toll-like receptor 4 (TLR4) is the principal receptor for bacterial endotoxin recognition, and functional variants in the gene confer endotoxin-hyporesponsiveness in humans. Furthermore, there is evidence that endotoxin exposure during early life is protective against the development of atopy and asthma, although this relationship remains poorly understood. It is therefore possible that genetic variation in the TLR4 locus contributes to asthma susceptibility. In this study we characterize the genetic diversity in the TLR4 locus and test for association between the common genetic variants and asthma-related phenotypes. In a cohort of 90 ethnically diverse subjects, we resequenced the TLR4 locus and identified a total of 29 single nucleotide polymorphisms. We assessed five common polymorphisms for evidence of association with asthma in two large family-based cohorts: a heterogeneous North American cohort (589 families), and a more homogenous population from northeastern Quebec, Canada (167 families). Using the transmission-disequilibrium test, we found no evidence of association for any of the polymorphisms tested, including two functional variants. Furthermore, we found no evidence for association between the TLR4 variants and four quantitative intermediate asthma- and atopy-related phenotypes. Based on these results, we found no evidence that genetic variation in TLR4 contributes to asthma susceptibility.

Original languageEnglish (US)
Pages (from-to)1449-1456
Number of pages8
JournalAmerican journal of respiratory and critical care medicine
Volume166
Issue number11
DOIs
StatePublished - Dec 1 2002

Keywords

  • Asthma
  • Genetic association
  • Genetics
  • Polymorphism
  • Toll-like receptor 4

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

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