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

Hum Genet. 2010 Feb;127(2):207-21. doi: 10.1007/s00439-009-0763-1. Epub 2009 Nov 10.

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-gamma, IL-2, IL-10, TNF-alpha, 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-alpha 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-alpha 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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Carrier Proteins / genetics
  • Child
  • Cytokines / metabolism*
  • DEAD Box Protein 58
  • DEAD-box RNA Helicases / genetics
  • DNA Topoisomerases, Type II / genetics
  • DNA-Binding Proteins / genetics
  • Female
  • Granulocyte-Macrophage Colony-Stimulating Factor / metabolism
  • Humans
  • Immunity, Cellular / genetics*
  • Immunity, Cellular / immunology*
  • Immunity, Innate / genetics
  • Immunity, Innate / immunology
  • Interleukin-10 / metabolism
  • Interleukin-2 / metabolism
  • Leukocytes, Mononuclear / cytology
  • Leukocytes, Mononuclear / immunology
  • Leukocytes, Mononuclear / metabolism
  • Male
  • Poly-ADP-Ribose Binding Proteins
  • Polymorphism, Single Nucleotide
  • Receptors, Retinoic Acid / genetics
  • Retinoic Acid Receptor alpha
  • Retinoid X Receptor alpha / genetics
  • Rubella Vaccine / immunology*
  • Toll-Like Receptor 3 / genetics
  • Tumor Necrosis Factor-alpha / metabolism
  • Young Adult

Substances

  • Carrier Proteins
  • Cytokines
  • DNA-Binding Proteins
  • Interleukin-2
  • Poly-ADP-Ribose Binding Proteins
  • RARA protein, human
  • Receptors, Retinoic Acid
  • Retinoic Acid Receptor alpha
  • Retinoid X Receptor alpha
  • Rubella Vaccine
  • TLR3 protein, human
  • Toll-Like Receptor 3
  • Tumor Necrosis Factor-alpha
  • retinoic acid receptor beta
  • retinoic acid receptor gamma
  • Interleukin-10
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • TRIM5 protein, human
  • DDX58 protein, human
  • DEAD Box Protein 58
  • DEAD-box RNA Helicases
  • DNA Topoisomerases, Type II
  • TOP2B protein, human