Background: Innate immune system stimuli, such as endotoxin, seem to affect allergy risk. Previously, we described gene-environment interactions between the endotoxin receptor polymorphism C-260T of the CD14 gene and endotoxin exposure on total serum IgE level; however, the mechanism of this interaction is not known. Objective: To examine whether this gene-environment interaction affects early CD4+Foxp3- or CD4+Foxp3 + lymphocyte numbers. Methods: Participating children were part of a birth cohort in the Detroit metropolitan area. Participants were genotyped for the CD14 C-260T polymorphism. Endotoxin exposure was estimated from dust measured in the home when children were 6 months old. Intracellular Foxp3 protein expression, a regulatory T-cell marker, was used to characterize CD4+ lymphocytes in blood samples collected at the age of 12 months; total serum IgE level was also measured at this time. Because race/ethnicity may confound or modify genetic associations, all analyses were stratified by race/ethnicity. Results: We observed a significant gene-environment interaction between CD14 C-260T genotype and endotoxin exposure on CD4+ lymphocyte numbers, particularly CD4+Foxp3- lymphocytes. Stratified analyses suggest effect modification by race/ethnicity on CD4 +Foxp3+ lymphocyte numbers, with a significant interaction in African American children but not in white children. The interaction between CD14 C-260T genotype and endotoxin exposure on total IgE levels was opposite that observed for CD4+ lymphocyte numbers, suggesting reciprocal relationships. Conclusions: A gene-environment interaction between endotoxin and CD14 C-260T genotype on IgE levels may be the result of an upstream, opposing effect on CD4+Foxp3+ and CD4+Foxp3- lymphocyte numbers. Race/ethnicity may affect which of these cell populations is affected by this gene-environment interaction.
ASJC Scopus subject areas
- Immunology and Allergy
- Pulmonary and Respiratory Medicine