title: SNP/haplotype associations in cytokine and cytokine receptor genes and immunity to rubella vaccine.
abstract: 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.
authors.affiliation: Mayo Clinic Vaccine Research Group, Mayo Clinic, Guggenheim 611C, 200 First Street SW, Rochester, MN 55905, USA.
authors.forename: Neelam
authors.initials: N
authors.lastname: Dhiman
authors.forename: Iana H
authors.initials: IH
authors.lastname: Haralambieva
authors.forename: Richard B
authors.initials: RB
authors.lastname: Kennedy
authors.forename: Robert A
authors.initials: RA
authors.lastname: Vierkant
authors.forename: Megan M
authors.initials: MM
authors.lastname: O'Byrne
authors.forename: Inna G
authors.initials: IG
authors.lastname: Ovsyannikova
authors.forename: Robert M
authors.initials: RM
authors.lastname: Jacobson
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Poland
mesh_terms: 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
chemical_list: 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