Parental smoking impairs vaccine responses in children with atopic genotypes.
BACKGROUND
Gene-environment interactions play central roles in controlling postnatal maturation of immune function, but their effects on infant vaccine responses are unknown. Genetic variants associated with atopy and the environmental factor of exposure to parental smoking (PS) of tobacco independently alter immune responses.


OBJECTIVE
We sought to investigate the hypothesis that genetic variants associated with atopy and their interaction with PS influence infant vaccine responsiveness.


METHODS
In 200 infants with parental atopic history, relationships were sought between polymorphisms in the IL-4, IL-4 receptor alpha (IL-4Ralpha), and IL-13 genes; PS; and immune responses to diphtheria/tetanus vaccination.


RESULTS
Analyses stratified by PS unmasked negative associations between atopic alleles of these genes and vaccine outcomes. The most consistent involved the IL-4Ralpha 551 QR/QQ genotypes, which were associated with reduced IgG levels (P = .02) and T-cell responses (IFN-gamma, P = .002; IL-10, P = .01; 1L-13, P = .01; IL-5, P = .06) to tetanus toxoid and parallel reductions in polyclonal T-cell responses and innate immune responses in PS-exposed infants.


CONCLUSIONS
PS potentiates suppressive effects of variants in immune response genes in children. These effects are not observed in the absence of this exposure. Ultimately, this finding might have implications for infant vaccination in countries with high smoking rates. It might also have broader implications in relation to environmental toxicology because it demonstrates specific mechanisms through which the developing immune system might be differentially sensitive to low-level toxicant exposures.


CONCLUSIONS
PS interacts with genes associated with atopy to impair vaccine responses. These interactions might have vaccine design and public health implications.
Baynam
Gareth
G
Telethon Institute for Child Health Research, Perth, Australia. garethb@ichr.uwa.edu.au <garethb@ichr.uwa.edu.au>
Khoo
Siew-Kim
SK
Rowe
Julie
J
Zhang
Guicheng
G
Laing
Ingrid
I
Hayden
Catherine
C
Kusel
Merci
M
DeKlerk
Nick
N
Sly
Peter
P
Goldblatt
Jack
J
Holt
Patrick
P
LeSouef
Peter
P
D000328:Adult; D002648:Child; D002675:Child, Preschool; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D006967:Hypersensitivity / Q000235:genetics*; D007113:Immunity, Innate; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D018793:Interleukin-13 / Q000235:genetics*; D015847:Interleukin-4 / Q000235:genetics*; D008297:Male; D010290:Parents; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D019948:Receptors, Interleukin-4 / Q000235:genetics*; D013601:T-Lymphocytes / Q000276:immunology; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*; D014612:Vaccines / Q000276:immunology*
D018793:Interleukin-13; D019948:Receptors, Interleukin-4; D014028:Tobacco Smoke Pollution; D014612:Vaccines; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma