TY - JOUR
T1 - Gene-environment interactions between CD14 C-260T and endotoxin exposure on Foxp3+ and Foxp3- CD4+ lymphocyte numbers and total serum IgE levels in early childhood
AU - Williams, L. Keoki
AU - Oliver, Jennifer
AU - Peterson, Edward L.
AU - Bobbitt, Kevin R.
AU - McCabe, Michael J.
AU - Smolarek, Derek
AU - Havstad, Suzanne L.
AU - Wegienka, Ganesa
AU - Burchard, Esteban G.
AU - Ownby, Dennis R.
AU - Johnson, Christine C.
N1 - Funding Information:
Funding Sources: This work was supported by grants from the Fund for Henry Ford Hospital and the National Institute of Allergy and Infectious Diseases ( AI61774, AI50681, AI59415 ) and the National Heart, Lung, and Blood Institute ( HL79055 ), National Institutes of Health.
PY - 2008/2
Y1 - 2008/2
N2 - 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.
AB - 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.
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U2 - 10.1016/S1081-1206(10)60421-8
DO - 10.1016/S1081-1206(10)60421-8
M3 - Article
C2 - 18320914
AN - SCOPUS:39049108442
SN - 1081-1206
VL - 100
SP - 128
EP - 136
JO - Annals of Allergy, Asthma and Immunology
JF - Annals of Allergy, Asthma and Immunology
IS - 2
ER -