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

L. Keoki Williams, Jennifer Oliver, Edward L. Peterson, Kevin R. Bobbitt, Michael J. McCabe, Derek Smolarek, Suzanne L. Havstad, Ganesa Wegienka, Esteban G. Burchard, Dennis Randall Ownby, Christine C. Johnson

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)128-136
Number of pages9
JournalAnnals of Allergy, Asthma and Immunology
Volume100
Issue number2
DOIs
StatePublished - Jan 1 2008

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Gene-Environment Interaction
Lymphocyte Count
Endotoxins
Immunoglobulin E
Serum
Genotype
Lymphocytes
Regulatory T-Lymphocytes
Dust
African Americans
Immune System
Hypersensitivity
Parturition
Population
Genes
Proteins

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Pulmonary and Respiratory Medicine

Cite this

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. / Williams, L. Keoki; Oliver, Jennifer; Peterson, Edward L.; Bobbitt, Kevin R.; McCabe, Michael J.; Smolarek, Derek; Havstad, Suzanne L.; Wegienka, Ganesa; Burchard, Esteban G.; Ownby, Dennis Randall; Johnson, Christine C.

In: Annals of Allergy, Asthma and Immunology, Vol. 100, No. 2, 01.01.2008, p. 128-136.

Research output: Contribution to journalArticle

Williams, L. Keoki ; Oliver, Jennifer ; Peterson, Edward L. ; Bobbitt, Kevin R. ; McCabe, Michael J. ; Smolarek, Derek ; Havstad, Suzanne L. ; Wegienka, Ganesa ; Burchard, Esteban G. ; Ownby, Dennis Randall ; Johnson, Christine C. / 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. In: Annals of Allergy, Asthma and Immunology. 2008 ; Vol. 100, No. 2. pp. 128-136.
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abstract = "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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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 Randall

AU - Johnson, Christine C.

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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.

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