TOLL-like receptor 10 genetic variation is associated with asthma in two independent samples

Ross Lazarus, Benjamin A. Raby, Christoph Lange, Edwin K. Silverman, David J. Kwiatkowski, Donata Vercelli, Walt J. Klimecki, Fernando D. Martinez, Scott T. Weiss

Research output: Contribution to journalArticle

119 Scopus citations

Abstract

TOLL-like receptor 10 (TLR10) is the most recently identified human homolog of the Drosophila TOLL protein. In humans, the TOLL-like receptors recognize pathogen-associated molecular patterns (PAMPs) as part of innate immune host defenses. Localized to chromosome 4p14, the specific ligands and functions of TLR10 are currently unknown, although it is expressed in lung and in B-lymphocytes. TLR10 is a potential asthma candidate gene because early life innate immune responses to ubiquitous inhaled allergens and PAMPs may influence asthma susceptibility. Resequencing in 47 subjects revealed a total of 78 single nucleotide polymorphisms (SNPS) (1 SNP per 106 bp) of which only 11 had been previously published. A significant association (p < = 0.02) between two SNPs (C.+1031G>A, c.+2322A>G) and physician-diagnosed asthma was observed in a case control study (517 cases, 519 control subjects) of European American subjects nested within the Nurses' Health Study cohort. The association for these same two SNPs (p ≤ 0.015) replicated in an independent family based cohort, where a measure of airway hyperresponsiveness (PC20) was also associated (p = 0.026 for c.+1031G>A). Consistent association in two independent samples and association with an intermediate phenotype provides strong support for TLR10 genetic variation contributing to asthma risk.

Original languageEnglish (US)
Pages (from-to)594-600
Number of pages7
JournalAmerican journal of respiratory and critical care medicine
Volume170
Issue number6
DOIs
StatePublished - Sep 15 2004

Keywords

  • Asthma
  • Single nucleotide polymorphisms
  • Toll-like receptor 10

ASJC Scopus subject areas

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

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