title: Replication of associations between cytokine and cytokine receptor single nucleotide polymorphisms and measles-specific adaptive immunophenotypic extremes.
abstract: Our objective was to replicate previously reported associations between cytokine and cytokine receptor SNPs and humoral and CMI (cell-mediated immune) responses to measles vaccine. All subjects (n=758) received two doses of MMR (measles/mumps/rubella) vaccine. From these subjects, candidate cytokine and cytokine receptor SNPs were genotyped and analyzed in 29-30 subjects falling into one of four "extreme" humoral (Ab(high/low)) and CMI (CMI(high/low)) response quadrants. Associations between seven SNPs (out of 11 in the discovery study) and measles-specific neutralizing antibody levels and IFN-γ ELISPOT responses were evaluated using chi-square tests. We found one replicated association for SNP rs372889 in the IL12RB1 gene (P=0.03 for Ab(high)CMI(high) vs. Ab(low)CMI(low)). Our findings demonstrate the importance of replicating genotypic-phenotypic associations, which can be achieved using immunophenotypic extremes and smaller sample sizes. We speculate that IL12RB1 polymorphisms may affect IL-12 and IL-23 binding and downstream effects, which are critical cytokines in the CMI response to measles vaccine.
authors.affiliation: Mayo Clinic Vaccine Research Group, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: White
authors.forename: Iana H
authors.initials: IH
authors.lastname: Haralambieva
authors.forename: Inna G
authors.initials: IG
authors.lastname: Ovsyannikova
authors.forename: Robert A
authors.initials: RA
authors.lastname: Vierkant
authors.forename: Megan M
authors.initials: MM
authors.lastname: O'Byrne
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Poland
mesh_terms: D000293:Adolescent; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D002648:Child; D005260:Female; D056726:Genetic Association Studies; D006239:Haplotypes; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects; D056724:Immunity, Humoral / Q000187:drug effects; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000097:blood / Q000276:immunology; D018664:Interleukin-12 / Q000097:blood / Q000276:immunology; D053759:Interleukin-23 / Q000097:blood / Q000276:immunology; D008297:Male; D008457:Measles / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D008459:Measles virus / Q000276:immunology*; D022542:Measles-Mumps-Rubella Vaccine / Q000008:administration & dosage / Q000276:immunology*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics / Q000276:immunology*; D053707:Receptors, Interleukin-12 / Q000235:genetics* / Q000276:immunology; D014611:Vaccination; D055815:Young Adult
chemical_list: D000914:Antibodies, Viral; C508438:IL12RB1 protein, human; D053759:Interleukin-23; D022542:Measles-Mumps-Rubella Vaccine; D053707:Receptors, Interleukin-12; D018664:Interleukin-12; D007371:Interferon-gamma