Opposite effects of CD14/-260 on serum IgE levels in children raised in different environments

Background: Most complex diseases are the result of interactions between polymorphisms in the genome and environmental exposures. Objective: We sought to investigate the previously reported association between a polymorphism in the promoter region of CD14 (CD14/-260C -> T) and serum IgE levels in relation to the environment to which children are exposed. Methods: In 624 children living in 2 rural communities in Europe, we compared total and specific serum IgE levels between the genotypes of CD14/-260 in relation to exposure to animals and in relation to house dust endotoxin. Results: We found that the C allele of CD14/-260 was associated with higher levels of both total and specific serum IgE to aeroallergens in children with regular contact with pets, whereas an association in the opposite direction was found in children with regular contact with stable animals. This modifying effect of animal exposure was not explained by levels of house dust endotoxin. However, in children with high levels of house dust endotoxin, the C allele was associated with less specific IgE, independently from animal exposure. Conclusion: Because CD14 is a pattern recognition receptor for microbial molecules, the results suggest that the type and concentrations of such molecules present in the environment strongly determine the direction of the association between CD14/-260 and serum markers of atopy.