Rubella vaccine-induced cellular immunity: Evidence of associations with polymorphisms in the Toll-like, vitamin A and D receptors, and innate immune response genes

Inna G. Ovsyannikova, Neelam Dhiman, Iana H. Haralambieva, Robert A. Vierkant, Megan M. O'Byrne, Robert M. Jacobson, Gregory A. Poland

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Abstract

Toll-like, vitamin A and D receptors and other innate proteins participate in various immune functions. We determined whether innate gene-sequence variations are associated with rubella vaccine-induced cytokine immune responses. We genotyped 714 healthy children (11-19 years of age) after two doses of rubella-containing vaccine for 148 candidate SNP markers. Rubella virus-induced cytokines were measured by ELISA. Twenty-two significant associations (range of P values 0.002-0.048) were found between SNPs in the vitamin A receptor family (RARA, RARB, TOP2B and RARG), vitamin D receptor and downstream mediator of vitamin D signaling (RXRA) genes and rubella virus-specific (IFN-γ, IL-2, IL-10, TNF-α, and GM-CSF) cytokine immune responses. A TLR3 gene promoter region SNP (rs5743305, -8441A > T) was associated with rubella-specific GM-CSF secretion. Importantly, SNPs in the TRIM5 gene coding regions, rs3740996 (His43Tyr) and rs10838525 (Gln136Arg), were associated with an allele dose-related secretion of rubella virus-specific TNF-α and IL-2/GM-CSF, respectively, and have been previously shown to have functional consequences regarding the antiviral activity and susceptibility to HIV-1 infection. We identified associations between individual SNPs and haplotypes in, or involving, the RIG-I (DDX58) gene and rubella-specific TNF-α secretion. This is the first paper to present evidence that polymorphisms in the TLR, vitamin A, vitamin D receptor, and innate immunity genes can influence adaptive cytokine responses to rubella vaccination.

Original languageEnglish (US)
Pages (from-to)207-221
Number of pages15
JournalHuman genetics
Volume127
Issue number2
DOIs
StatePublished - Jan 1 2010

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ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Ovsyannikova, I. G., Dhiman, N., Haralambieva, I. H., Vierkant, R. A., O'Byrne, M. M., Jacobson, R. M., & Poland, G. A. (2010). Rubella vaccine-induced cellular immunity: Evidence of associations with polymorphisms in the Toll-like, vitamin A and D receptors, and innate immune response genes. Human genetics, 127(2), 207-221. https://doi.org/10.1007/s00439-009-0763-1