SNP/haplotype associations in cytokine and cytokine receptor genes and immunity to rubella vaccine.
An effective immune response to vaccination is, in part, a complex interaction of alleles of multiple genes regulating cytokine networks. We conducted a genotyping study of Th1/Th2/inflammatory cytokines/cytokine receptors in healthy children (n = 738, 11-19 years) to determine associations between individual single-nucleotide polymorphisms (SNPs)/haplotypes and immune outcomes after two doses of rubella vaccine. SNPs (n = 501) were selected using the ldSelect-approach and genotyped using Illumina GoldenGate and TaqMan assays. Rubella-IgG levels were measured by immunoassay and secreted cytokines by ELISA. Linear regression and post hoc haplotype analyses were used to determine associations between single SNPs/haplotypes and immune outcomes. Increased carriage of minor alleles for the promoter SNPs (rs2844482 and rs2857708) of the TNFA gene were associated with dose-related increases in rubella antibodies. IL-6 secretion was co-directionally associated (p < or = 0.01) with five intronic SNPs in the TNFRSF1B gene in an allele dose-related manner, while five promoter/intronic SNPs in the IL12B gene were associated with variations in IL-6 secretion. TNFA haplotype AAACGGGGC (t-statistic = 3.32) and IL12B promoter haplotype TAG (t-statistic = 2.66) were associated with higher levels of (p < or = 0.01) rubella-IgG and IL-6 secretion, respectively. We identified individual SNPs/haplotypes in TNFA/TNFRSF1B and IL12B genes that appear to modulate immunity to rubella vaccination. Identification of such "genetic fingerprints" may predict the outcome of vaccine response and inform new vaccine strategies.
Dhiman
Neelam
N
Mayo Clinic Vaccine Research Group, Mayo Clinic, Guggenheim 611C, 200 First Street SW, Rochester, MN 55905, USA.
Haralambieva
Iana H
IH
Kennedy
Richard B
RB
Vierkant
Robert A
RA
O'Byrne
Megan M
MM
Ovsyannikova
Inna G
IG
Jacobson
Robert M
RM
Poland
Gregory A
GA
D000293:Adolescent; D000328:Adult; D000914:Antibodies, Viral / Q000097:blood; D002648:Child; D016207:Cytokines / Q000235:genetics*; D005260:Female; D006239:Haplotypes; D006801:Humans; D007111:Immunity, Cellular; D007074:Immunoglobulin G / Q000097:blood; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011401:Promoter Regions, Genetic; D018121:Receptors, Cytokine / Q000235:genetics*; D012409:Rubella / Q000235:genetics / Q000276:immunology*; D012411:Rubella Vaccine / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology; D014611:Vaccination; D055815:Young Adult
D000914:Antibodies, Viral; D016207:Cytokines; D007074:Immunoglobulin G; D015850:Interleukin-6; D018121:Receptors, Cytokine; D012411:Rubella Vaccine; D014409:Tumor Necrosis Factor-alpha; C040901:rubella antibodies