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

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.

Key words: CD14, endotoxin, LPS, asthma, allergy, atopy, asthma severity, IgE, genetics, gene-environment interaction

Abbreviations used: ASQ, Asthma severity questionnaire, EU, Endotoxin unit, FBAT, Family-Based Association Test, FVC, Forced vital capacity, HDE, House dust endotoxin, LD, Linkage disequilibrium, OR, Odds ratio, sCD14, Soluble CD14, SNP, Single nucleotide polymorphism, tIgE, Total IgE