Associations between measles vaccine immunity and single-nucleotide polymorphisms in cytokine and cytokine receptor genes.
BACKGROUND
Cytokines are key regulators of measles vaccine humoral and cellular immunity. Single-nucleotide polymorphisms (SNPs) that are associated with differences in cytokine levels should also influence measles vaccine-induced immunity.


METHODS
We genotyped 118 measles-mumps-rubella-vaccinated subjects for SNPs from 6 cytokine genes (interleukin [IL]-2, IL-4, IL-10, IL-12A, IL-12B, and interferon [IFN]-gamma) and their receptors (IL-2RA, IL-2RB, IL-4RA, IL-10RA, IL-10RB, IL-12RB1, IL-12RB2, and IFN-gamma R). Associations of SNPs with measles-specific antibodies, lymphoproliferation, and secreted cytokines were determined using chi2 tests and analyses of covariance.


RESULTS
We found significant associations (P<.05) between SNPs in the IL-2, IL-10, and IL-12RB genes and measles vaccine-induced immunity. The IVS1-100G (rs2069762) and the Ex2-34G (rs2069763) SNPs within the IL-2 gene were associated with high antibody and high lymphoproliferative responses, whereas SNPs within the IL-10 and IL-12R genes were associated with low antibody and lymphoproliferative responses to measles. SNPs within the IL-4RA and IL-12B genes varied significantly (P<.05) across immune response measures. Significant associations were also found between SNPs and secreted cytokine levels.


CONCLUSIONS
Specific SNPs in the cytokine and cytokine receptor genes are significantly associated with variations in measures of the immune response to measles vaccination. These results need to be further validated in a larger cohort.
Dhiman
Neelam
N
Mayo Vaccine Research Group, Mayo Clinic, Rochester, MN 55905, USA.
Ovsyannikova
Inna G
IG
Cunningham
Julie M
JM
Vierkant
Robert A
RA
Kennedy
Richard B
RB
Pankratz
V Shane
VS
Poland
Gregory A
GA
Jacobson
Robert M
RM
D016207:Cytokines / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D005838:Genotype; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D008458:Measles Vaccine / Q000235:genetics / Q000276:immunology*; D008459:Measles virus / Q000276:immunology*; D020641:Polymorphism, Single Nucleotide; D018121:Receptors, Cytokine / Q000235:genetics / Q000502:physiology*
D016207:Cytokines; D008458:Measles Vaccine; D018121:Receptors, Cytokine; D007371:Interferon-gamma