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 language | English (US) |
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Pages (from-to) | 1203-1209 |
Number of pages | 7 |
Journal | Journal of Allergy and Clinical Immunology |
Volume | 115 |
Issue number | 6 |
DOIs | |
State | Published - Jun 2005 |
Keywords
- Allergy
- Asthma
- Asthma severity
- Atopy
- CD14
- Endotoxin
- Gene-environment interaction
- Genetics
- IgE
- LPS
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology