title: Genetic variation in IL18R1 and IL18 genes and Inteferon γ ELISPOT response to smallpox vaccination: an unexpected relationship.
abstract: BACKGROUND
  Genetic association studies demonstrated a role for cytokine proteins and cytokine or cytokine receptor gene polymorphisms in smallpox vaccine-induced adaptive immunity.
  
  
  METHODS
  We examined the association of genetic polymorphisms with cellular (interferon [IFN] γ enzyme-linked immunospot assay [ELISPOT]) immune response to smallpox vaccine in 1076 immunized individuals.
  
  
  RESULTS
  The majority of significant associations were discovered between single-nucleotide polymorphisms/haplotypes in IL18R1 and IL18 genes, in which we previously reported an association with vaccinia virus-induced neutralizing antibody titers in this study cohort. A functional coding IL18R1 polymorphism (rs1035130/Phe251Phe; P = .01) was significantly associated with an allele dose-related increase in IFN-γ production and was also associated with vaccinia-specific neutralizing antibody titers. Significant associations were also found between IL18R1 haplotypes and variations in IFN-γ ELISPOT responses (global P < .0001).
  
  
  CONCLUSIONS
  Our data suggest the importance of variants in the IL18R1 and IL18 genetic loci for broad-based smallpox vaccine-induced adaptive immunity.
authors.affiliation: Mayo Clinic Vaccine Research Group.
authors.forename: Inna G
authors.initials: IG
authors.lastname: Ovsyannikova
authors.forename: Iana H
authors.initials: IH
authors.lastname: Haralambieva
authors.forename: Richard B
authors.initials: RB
authors.lastname: Kennedy
authors.forename: Megan M
authors.initials: MM
authors.lastname: O'Byrne
authors.forename: V Shane
authors.initials: VS
authors.lastname: Pankratz
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Poland
mesh_terms: D056704:Adaptive Immunity; D000293:Adolescent; D000328:Adult; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D056726:Genetic Association Studies; D006239:Haplotypes; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics*; D020382:Interleukin-18 / Q000235:genetics*; D053727:Interleukin-18 Receptor alpha Subunit / Q000235:genetics*; D007438:Introns; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D017422:Sequence Analysis, DNA; D012900:Smallpox Vaccine / Q000276:immunology*; D014611:Vaccination; D014615:Vaccinia / Q000517:prevention & control*; D055815:Young Adult
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; C508572:IL18R1 protein, human; D020382:Interleukin-18; D053727:Interleukin-18 Receptor alpha Subunit; D012900:Smallpox Vaccine; D007371:Interferon-gamma
keywords: African-Americans; Polymorphism; enzyme-linked immunospot assay; european continental ancestry group; genetic predisposition to disease; genetic variation; haplotypes; interferon-gamma; interleukin-18; interleukin-18 receptor alpha subunit; single nucleotide; smallpox vaccine; vaccinia virus; viral vaccines
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