Association between farm exposure and atopy, according to the CD14 C-159T polymorphism

BACKGROUND: A higher exposure to bacterial compounds is purported to explain the lower prevalence of allergy in farm children, but responsiveness to bacterial compounds is modulated by genetic factors. OBJECTIVE: To assess whether the protective effect of farm exposure on atopy is influenced by a CD14 promoter functional polymorphism. METHODS: We administered a detailed questionnaire on farm exposure in childhood and genotyped the CD14 C-159T polymorphism in 2 French centers participating in the European Community Respiratory Health Survey (ECRHS)-II. RESULTS: Six hundred randomly selected young adults provided blood samples for IgE measurements and had CD14 C-159T genotyped. Exposure to a farming environment in early life was associated with a reduced risk of nasal allergies (odds ratio [OR], 0.54; 95% CI, 0.29-1.00) and atopic sensitization (OR, 0.47; 95% CI, 0.24-0.93) in adulthood. A lower risk of allergic rhinitis and atopy was also observed in carriers of the CD14-159TT genotype compared with -159CC subjects (OR, 0.52; 95% CI, 0.30-0.88; and OR, 0.54; 95% CI, 0.31-0.92, respectively). When farm exposure and CD14 C-159T were considered together, the risk of nasal allergies and atopy was the most reduced in the subjects who combined both an early-life exposure to a farming environment and the -159TT genotype (OR, 0.26; 95% CI, 0.07-0.94; and OR, 0.21; 95% CI, 0.05-0.93, respectively, vs nonexposed -159CC+CT subjects). The results were consistent in the 2 centers, supporting the validity of the results. CONCLUSION: A gene-by-environment interaction between CD14 C-159T and environmental exposure in childhood may modify the development of atopy. CLINICAL IMPLICATIONS: This polymorphism should be considered in interventions studies that use microbial stimuli to reduce sensitization.