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

Authors: Zambelli-Weiner, A  Ehrlich, E  Stockton, ML  Grant, AV  Zhang, S  Levett, PN  Beaty, TH  Barnes, KC 
Citation: Zambelli-Weiner A, etal., J Allergy Clin Immunol. 2005 Jun;115(6):1203-9.
Pubmed: (View Article at PubMed) PMID:15940135
DOI: Full-text: DOI:10.1016/j.jaci.2005.03.001

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.

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CRRD Object Information
CRRD ID: 4144814
Created: 2010-10-15
Species: All species
Last Modified: 2010-10-15
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.