title: Associations between single nucleotide polymorphisms and haplotypes in cytokine and cytokine receptor genes and immunity to measles vaccination.
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.
authors.affiliation: Mayo Clinic Vaccine Research Group, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Iana H
authors.initials: IH
authors.lastname: Haralambieva
authors.forename: Inna G
authors.initials: IG
authors.lastname: Ovsyannikova
authors.forename: Richard B
authors.initials: RB
authors.lastname: Kennedy
authors.forename: Robert A
authors.initials: RA
authors.lastname: Vierkant
authors.forename: V Shane
authors.initials: VS
authors.lastname: Pankratz
authors.forename: Robert M
authors.initials: RM
authors.lastname: Jacobson
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Poland
mesh_terms: D000293:Adolescent; D057134:Antibodies, Neutralizing / Q000276:immunology; D000914:Antibodies, Viral / Q000276:immunology; D002648:Child; D016207:Cytokines / Q000235:genetics* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D058501:Enzyme-Linked Immunospot Assay; D005006:Ethnicity; D005260:Female; D056726:Genetic Association Studies; D006239:Haplotypes; D006801:Humans; D008214:Lymphocytes / Q000276:immunology; D008297:Male; D008457:Measles / Q000276:immunology / Q000517:prevention & control*; D008459:Measles virus / Q000276:immunology*; D022542:Measles-Mumps-Rubella Vaccine / Q000008:administration & dosage / Q000276:immunology*; D020641:Polymorphism, Single Nucleotide; D018121:Receptors, Cytokine / Q000235:genetics*; D013334:Students; D055815:Young Adult
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D016207:Cytokines; D022542:Measles-Mumps-Rubella Vaccine; D018121:Receptors, Cytokine