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- Title
SNP/haplotype associations in cytokine and cytokine receptor genes and immunity to rubella vaccine.
- Authors
Dhiman, Neelam; Haralambieva, Iana H.; Kennedy, Richard B.; Vierkant, Robert A.; O’Byrne, Megan M.; Ovsyannikova, Inna G.; Jacobson, Robert M.; Poland, Gregory A.
- 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 ≤ 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 ≤ 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.
- Subjects
GENETIC polymorphisms; CYTOKINES; CELLULAR immunity; CELL receptors; IMMUNITY; RUBELLA vaccines
- Publication
Immunogenetics, 2010, Vol 62, Issue 4, p197
- ISSN
0093-7711
- Publication type
Article
- DOI
10.1007/s00251-010-0423-6