Associations between single nucleotide polymorphisms and haplotypes in cytokine and cytokine receptor genes and immunity to measles vaccination

Iana H. Haralambieva, Inna G. Ovsyannikova, Richard B. Kennedy, Robert A. Vierkant, V. Shane Pankratz, Robert M. Jacobson, Gregory A. Poland

Research output: Contribution to journalArticle

49 Scopus citations

Abstract

Identification of host genetic determinants of measles vaccine-induced immunity can be used to design better vaccines and ultimately predict immune responses to vaccination.We performed a comprehensive candidate gene association study across 801 genetic markers in 56 cytokine/cytokine receptor genes, in a racially diverse cohort of 745 schoolchildren after two doses of MMR vaccine. Using linear regression methodologies we examined associations between SNPs/haplotypes and measles virus-specific immunity.Forty-eight significant SNP associations with variations in neutralizing antibodies and measles-specific IFNγ Elispot responses were identified (p<. 0.05). Our study replicated an important previously found association of a functional IL12B genetic variant rs3212227 with variations in measles-specific humoral immunity (p= 0.037). Similarly, two previously reported promoter IL10 and IL2 polymorphisms (rs1800890 and rs2069762) demonstrated associations with measles-specific cellular immunity in Caucasians (p≤. 0.034). Multiple IL7R polymorphisms, including a non-synonymous functional SNP (rs6897932/Thr244Ile), were associated with humoral (p≤. 0.024) and/or cellular (IFNγ Elispot, p≤. 0.023) measles-specific immune responses in Caucasians, but not African-Americans. Haplotype level analysis confirmed the association of IL7R genetic variants with measles vaccine-induced immunity in the Caucasian group (global p-value = 0.003).Our results validate previous findings and identify new plausible genetic determinants, including IL7R polymorphisms, regulating measles vaccine-induced immunity in a race-specific manner.

Original languageEnglish (US)
Pages (from-to)7883-7895
Number of pages13
JournalVaccine
Volume29
Issue number45
DOIs
StatePublished - Oct 19 2011

Keywords

  • Cytokine
  • Cytokine receptor
  • 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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