Effects of vitamin A and D receptor gene polymorphisms/haplotypes on immune responses to measles vaccine

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

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

Objective: Vitamins A and D, and their receptors, are important regulators of the immune system, including vaccine immune response. We assessed the association between polymorphisms in the vitamin A receptors [retinoic acid receptor α, retinoic acid receptor β (RARB), and retinoic acid receptor γ] and vitamin D receptor (VDR)/retinoid X receptor α (RXRA) genes and interindividual variations in immune responses after two doses of measles vaccine in 745 children. Methods: Using a tag single nucleotide polymorphism (SNP) approach, we genotyped 745 healthy children for the 391 polymorphisms in vitamin A receptor and VDR genes. Results: The RARB haplotype (rs6800566/rs6550976/rs9834818) was significantly associated with variations in both measles antibody (global, P=0.013) and cytokine secretion levels, such as interleukin (IL)-10 (global, P=0.006), interferon (IFN)-α (global, P=0.008), and tumor necrosis factor-α (global, P=0.039) in the Caucasian subgroup. Specifically, the RARB haplotype, AAC, was associated with higher (t-statistic: 3.27, P=0.001) measles antibody levels. At the other end of the spectrum, haplotype GG for rs6550978/rs6777544 was associated with lower antibody levels (t-statistic:-2.32, P=0.020) in the Caucasian subgroup. In a sensitivity analysis, the RARB haplotype, CTGGGCAA, remained marginally significant (P<0.02) when the single SNP rs12630816 was included in the model for IL-10 secretion levels. A significant association was found between lower measles-specific IFN-γ Enzyme-linked immunosorbent spot responses and haplotypes rs11102986/rs11103473/rs11103482/rs10776909/rs12004589/rs35780541/ rs2266677/rs875444 (global, P=0.004) and rs6537944/rs3118571 (global, P<0.001) in the RXRA gene for Caucasians. We also found associations between multiple RARB, VDR, and RXRA SNPs/haplotypes and measles-specific IL-2, IL-6, IL-10, IFN-α, IFN-γ, IFNλ-1, and TNF-α cytokine secretions. Conclusion: Our results suggest that specific allelic variations and haplotypes in the vitamin A receptor and VDR genes may influence adaptive immune responses to measles vaccine.

Original languageEnglish (US)
Pages (from-to)20-31
Number of pages12
JournalPharmacogenetics and genomics
Volume22
Issue number1
DOIs
StatePublished - Jan 1 2012

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Keywords

  • genes
  • immunogenetics
  • measles vaccine immunity
  • single nucleotide polymorphisms
  • vitamin A receptor
  • vitamin D receptor

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Genetics(clinical)

Cite this

Ovsyannikova, I. G., Haralambieva, I. H., Vierkant, R. A., O'Byrne, M. M., Jacobson, R. M., & Poland, G. A. (2012). Effects of vitamin A and D receptor gene polymorphisms/haplotypes on immune responses to measles vaccine. Pharmacogenetics and genomics, 22(1), 20-31. https://doi.org/10.1097/FPC.0b013e32834df186