title: Single-nucleotide polymorphism associations in common with immune responses to measles and rubella vaccines.
abstract: Single-nucleotide polymorphisms (SNPs) in candidate immune response genes were evaluated for associations with measles- and rubella-specific neutralizing antibodies, interferon (IFN)-γ, and interleukin (IL)-6 secretion in two separate association analyses in a cohort of healthy immunized subjects. We identified six SNP associations shared between the measles-specific and rubella-specific immune responses, specifically neutralizing antibody titers (DDX58), secreted IL-6 (IL10RB, IL12B), and secreted IFN-γ (IFNAR2, TLR4). An intronic SNP (rs669260) in the antiviral innate immune receptor gene, DDX58, was significantly associated with increased neutralizing antibody titers for both measles and rubella viral antigens post-MMR vaccination (p values 0.02 and 0.0002, respectively). Significant associations were also found between IL10RB (rs2284552; measles study p value 0.006, rubella study p value 0.00008) and IL12B (rs2546893; measles study p value 0.005, rubella study p value 0.03) gene polymorphisms and variations in both measles- and rubella virus-specific IL-6 responses. We also identified associations between individual SNPs in the IFNAR2 and TLR4 genes that were associated with IFN-γ secretion for both measles and rubella vaccine-specific immune responses. These results are the first to indicate that there are SNP associations in common across measles and rubella vaccine immune responses and that SNPs from multiple genes involved in innate and adaptive immune response regulation may contribute to the overall human antiviral response.
authors.affiliation: Mayo Clinic Vaccine Research Group, Mayo Clinic, Guggenheim 611C, 200 1st Street S.W., Rochester, MN, 55905, USA.
authors.forename: Inna G
authors.initials: IG
authors.lastname: Ovsyannikova
authors.forename: Hannah M
authors.initials: HM
authors.lastname: Salk
authors.forename: Beth R
authors.initials: BR
authors.lastname: Larrabee
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 / Q000235:genetics* / Q000276:immunology; D000293:Adolescent; D057134:Antibodies, Neutralizing / Q000378:metabolism; D000914:Antibodies, Viral / Q000276:immunology; D000956:Antigens, Viral / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D005260:Female; D056726:Genetic Association Studies / Q000379:methods; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics* / Q000276:immunology; D007223:Infant; D008297:Male; D008457:Measles / Q000235:genetics / Q000276:immunology*; D008458:Measles Vaccine / Q000276:immunology*; D008459:Measles virus / Q000276:immunology; D020641:Polymorphism, Single Nucleotide / Q000235:genetics* / Q000276:immunology; D012409:Rubella / Q000235:genetics / Q000276:immunology*; D012411:Rubella Vaccine / Q000276:immunology*; D012412:Rubella virus / Q000276:immunology
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D000956:Antigens, Viral; D008458:Measles Vaccine; D012411:Rubella Vaccine