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

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

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.

Virtual Health Library

Caribbean

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