CD14, endotoxin, and asthma risk: Actions and interactions

Research output: Contribution to journalArticle

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Abstract

A functional single nucleotide polymorphism in the 5 genomic region of CD14 (CD14/-159) is one of the most widely tested genetic variations in relation to asthma and associated traits. The results of these studies have shown a remarkable, statistically significant heterogeneity, with some studies indicating the T-allele as a risk factor, others the C-allele, and others finding no association. Recent studies in which exposure to house-dust endotoxin or to domestic sources of microbial exposure were assessed concomitantly with CD14/-159 have shown a consistent, replicable gene-environment interaction. Specifically, results suggest that the C-allele is a risk factor for allergic phenotypes at low levels of exposure, whereas the T-allele is a risk factor at high levels of exposure. This finding seems to be explained by a genetically-determined heterogeneity for the protective effect of microbial exposure on allergic phenotypes, with homozygotes for the C-allele showing a much stronger negative association between exposure and allergic outcomes than carries of the other two genotypes. These results suggest that the often encountered, limited replicability of genetic associations may, at least in part, be due to complex interactions between genes and environment in determining asthma-related outcomes.

Original languageEnglish (US)
Pages (from-to)221-225
Number of pages5
JournalProceedings of the American Thoracic Society
Volume4
Issue number3
DOIs
StatePublished - Jul 1 2007

Keywords

  • Asthma
  • CD14
  • Gene-environment interaction

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

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