Genetic polymorphisms in host antiviral genes: Associations with humoral and cellular immunity to measles vaccine

Iana H. Haralambieva, Inna G. Ovsyannikova, Benjamin J. Umlauf, Robert A. Vierkant, V. Shane Pankratz, Robert M. Jacobson, Gregory A. Poland

Research output: Contribution to journalArticlepeer-review

48 Scopus citations

Abstract

Host antiviral genes are important regulators of antiviral immunity and plausible genetic determinants of immune response heterogeneity after vaccination. We genotyped and analyzed 307 common candidate tagSNPs from 12 antiviral genes in a cohort of 745 schoolchildren immunized with two doses of measles-mumps-rubella (MMR) vaccine. Associations between SNPs/haplotypes and measles virus-specific immune outcomes were assessed using linear regression methodologies in Caucasians and African-Americans.Genetic variants within the DDX58/RIG-I gene, including a coding polymorphism (rs3205166/Val800Val), were associated as single-SNPs (p≤ 0.017; although these SNPs did not remain significant after correction for false discovery rate/FDR) and in haplotype-level analysis, with measles-specific antibody variations in Caucasians (haplotype allele p-value = 0.021; haplotype global p-value = 0.076). Four DDX58 polymorphisms, in high LD, demonstrated also associations (after correction for FDR) with variations in both measles-specific IFN-γ and IL-2 secretion in Caucasians (p≤ 0.001, q= 0.193). Two intronic OAS1 polymorphisms, including the functional OAS1 SNP rs10774671 (p= 0.003), demonstrated evidence of association with a significant allele-dose-related increase in neutralizing antibody levels in African-Americans. Genotype and haplotype-level associations demonstrated the role of ADAR genetic variants, including a non-synonymous SNP (rs2229857/Arg384Lys; p= 0.01), in regulating measles virus-specific IFN-γ Elispot responses in Caucasians (haplotype global p-value = 0.017). After correction for FDR, 15 single-SNP associations (11 SNPs in Caucasians and 4 SNPs in African-Americans) still remained significant at the q-value < 0.20.In conclusion, our findings strongly point to genetic variants/genes, involved in antiviral sensing and antiviral control, as critical determinants, differentially modulating the adaptive immune responses to live attenuated measles vaccine in Caucasians and African-Americans.

Original languageEnglish (US)
Pages (from-to)8988-8997
Number of pages10
JournalVaccine
Volume29
Issue number48
DOIs
StatePublished - Nov 8 2011

Keywords

  • Antiviral genes
  • Haplotypes
  • Immunity
  • Measles vaccine
  • Single nucleotide polymorphisms

ASJC Scopus subject areas

  • Molecular Medicine
  • Immunology and Microbiology(all)
  • veterinary(all)
  • Public Health, Environmental and Occupational Health
  • Infectious Diseases

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