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.
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.
Williams
L Keoki
LK
Department of Internal Medicine, Henry Ford Health System, Detroit, Michigan 48202, USA. kwillia5@hfhs.org
Oliver
Jennifer
J
Peterson
Edward L
EL
Bobbitt
Kevin R
KR
McCabe
Michael J
MJ
Smolarek
Derek
D
Havstad
Suzanne L
SL
Wegienka
Ganesa
G
Burchard
Esteban G
EG
Ownby
Dennis R
DR
Johnson
Christine C
CC
D000328:Adult; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D016022:Case-Control Studies; D002450:Cell Communication / Q000235:genetics* / Q000276:immunology*; D015331:Cohort Studies; D004391:Dust / Q000276:immunology; D004731:Endotoxins / Q000009:adverse effects*; D005260:Female; D051858:Forkhead Transcription Factors / Q000096:biosynthesis* / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D007073:Immunoglobulin E / Q000096:biosynthesis / Q000097:blood*; D007223:Infant; D018950:Lipopolysaccharide Receptors / Q000235:genetics*; D008137:Longitudinal Studies; D008297:Male; D020641:Polymorphism, Single Nucleotide
D004391:Dust; D004731:Endotoxins; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D018950:Lipopolysaccharide Receptors; D007073:Immunoglobulin E