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

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.

• Authors: April Zambelli-Weiner, Eva Ehrlich, Maria L Stockton, Audrey V Grant, Shu Zhang, Paul N Levett, Terri H Beaty, Kathleen C Barnes
• Journal: The Journal of allergy and clinical immunology (J Allergy Clin Immunol) Vol. 115 Issue 6 Pg. 1203-9 (Jun 2005) ISSN: 0091-6749 [Print] United States
• PMID: 15940135 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Dust
• Endotoxins
• Lipopolysaccharide Receptors

Topics

• Adult
• Asthma (etiology, genetics)
• Barbados
• Case-Control Studies
• Dust (analysis)
• Endotoxins (analysis)
• Family Characteristics
• Female
• Genotype
• Humans
• Lipopolysaccharide Receptors (genetics)
• Male
• Polymorphism, Genetic