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 < or = 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 < or = 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.
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Authors | Ross Lazarus, Benjamin A Raby, Christoph Lange, Edwin K Silverman, David J Kwiatkowski, Donata Vercelli, Walt J Klimecki, Fernando D Martinez, Scott T Weiss |
Journal | American journal of respiratory and critical care medicine
(Am J Respir Crit Care Med)
Vol. 170
Issue 6
Pg. 594-600
(Sep 15 2004)
ISSN: 1073-449X [Print] United States |
PMID | 15201134
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Receptors, Cell Surface
- TLR10 protein, human
- Toll-Like Receptor 10
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Topics |
- Black or African American
(genetics)
- Asthma
(complications, genetics, immunology)
- Bronchial Hyperreactivity
(genetics, immunology)
- Case-Control Studies
- Genetic Predisposition to Disease
(genetics)
- Genetic Variation
(genetics)
- Genotype
- Humans
- Immunity, Innate
(genetics)
- Phenotype
- Polymorphism, Genetic
- Receptors, Cell Surface
(genetics)
- Toll-Like Receptor 10
- United States
- White People
(genetics)
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