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

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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.

Section snippets

Study population

The population of Barbados is primarily of African descent with approximately 25% European admixture, similar to that observed in African Americans.18 Families were recruited in Barbados as a part of an ongoing asthma genetics study initiated in 1993.19, 20 Briefly, asthmatic probands were recruited from all regions of the island, including 6 polyclinics, 2 private clinics, and the Accident and Emergency Department of Queen Elizabeth Hospital. Patients with a positive family history of asthma

Subject characteristics and genotype data

Baseline characteristics of the study population by asthma status (and ignoring family structure) are summarized in Table I. There was no sex difference between subjects with and without asthma; however, subjects without asthma were, on average, twice as old as subjects with asthma. Given that this sample consists of families recruited through children with asthma and their parents, such an age difference is expected. Also as expected, subjects with asthma had a significantly higher asthma

Discussion

Individuals of African descent are at increased risk for asthma and atopic disease compared with European and European-American populations, and they have a more severe disease, even after controlling for factors such as access to medical care and socioeconomic status. Differences in genetic risk factors may contribute to these health disparities. We genotyped 747 individuals from 125 pedigrees (327 nuclear families) for the CD14-260 polymorphism and found the frequency of the -260T allele was

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    Supported by National Institutes of Health grant A120059, Allergy and Asthma Foundation of America Young Investigator Award (K.C.B.). K.C.B. was supported in part by the Mary Beryl Patch Turnbull Scholar Program. Dr Zambelli-Weiner was supported by a training grant in Environmental Health Sciences (T32 ESO7141) from the Johns Hopkins Bloomberg School of Public Health.

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