Evaluation of the CD14/-260 polymorphism and house dust endotoxin exposure in the Barbados Asthma Genetics Study

April Zambelli-Weiner, Eva Ehrlich, Maria L. Stockton, Audrey V. Grant, Shu Zhang, Paul N. Levett, Terri H. Beaty, Kathleen C. Barnes

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Both a functional promoter polymorphism in the gene encoding CD14 (C-260T) and exposure to endotoxin are believed to play key roles in modulating the immune response and expression of atopic disease. Objective: We aimed to evaluate the role of the CD14 C-260T polymorphism in a population of African descent and to test for interaction between this genotype and house dust endotoxin (HDE) exposure on atopic phenotypes. Methods: Asthmatic probands and their families were recruited as part of the Barbados Asthma Genetics Study. The C-260T polymorphism and two additional CD14 promoter markers (G-1461T, C-1721T) were genotyped. Endotoxin was measured in house dust samples. Results: Using a Family-Based Association Test, the C-260T allele appeared to be protective against asthma (z = -2.444; P =. 015) and asthma severity (z = -2.615; P =. 009) under a recessive model. No significant associations were observed for the G-1461T and C-1721T markers both individually and in haplotypes. In a case-control analysis, the CD14 TT genotype was found to reduce risk of asthma compared with the CD14 CC/CT genotypes (odds ratio [OR], 0.26; 95% CI, 0.14-0.49) and was associated with lower asthma severity scores (P <. 002). The TT genotype might protect against asthma for individuals with low HDE (OR, 0.09; 95% CI, 0.03-0.24), but may be a risk factor for individuals with high HDE (OR, 11.66; 95% CI, 1.03-131.7), suggesting a gene-environment interaction. Conclusion: These data suggest that the CD14-260 polymorphism may play a role in controlling risk to atopic disease and underscore the importance of incorporating key environmental exposures into studies of genetic risk factors.

Original languageEnglish (US)
Pages (from-to)1203-1209
Number of pages7
JournalJournal of Allergy and Clinical Immunology
Volume115
Issue number6
DOIs
StatePublished - Jun 2005

Keywords

  • Allergy
  • Asthma
  • Asthma severity
  • Atopy
  • CD14
  • Endotoxin
  • Gene-environment interaction
  • Genetics
  • IgE
  • LPS

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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