title: Impact of cytokine and cytokine receptor gene polymorphisms on cellular immunity after smallpox vaccination.
abstract: We explored associations between SNPs in cytokine/cytokine receptor genes and cellular immunity in subjects following primary smallpox vaccination. We also analyzed the genotype-phenotype associations discovered in the Caucasian subjects among a cohort of African-Americans. In Caucasians we found 277 associations (p<0.05) between gene SNPs and inter-individual variations in IFN-α, IL-12p40, IL-1β, IL-2, and TNF-α secretion levels. A collection of SNPs in the IL1RN, IL2RB, IL4R, IL6, IL10RB, IL12A, and IL12RB2 genes had consistent associations among both Caucasians and African-Americans. A regulatory SNP (rs452204) in the IL1RN gene was significantly associated with higher levels of IL-2 secretion in an allele dose-dependent manner in both race groups (p=0.05 for Caucasians and p=0.002 for African-Americans). IL12RB2 polymorphism rs3790567 was associated with a dose-related decrease in IL-1β secretion (p=0.009 for Caucasians and p=0.01 for African-Americans). Our results demonstrate that variations in smallpox vaccine-induced cytokine responses are modulated by genetic polymorphisms in cytokine and cytokine receptor genes.
authors.affiliation: Mayo Clinic Vaccine Research Group, Mayo Clinic, Rochester, MN 55905, USA.
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: V Shane
authors.initials: VS
authors.lastname: Pankratz
authors.forename: Robert A
authors.initials: RA
authors.lastname: Vierkant
authors.forename: Robert M
authors.initials: RM
authors.lastname: Jacobson
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Poland
mesh_terms: D000328:Adult; D001741:Black or African American / Q000235:genetics; D016207:Cytokines / Q000235:genetics* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007111:Immunity, Cellular; D053590:Interleukin 1 Receptor Antagonist Protein / Q000235:genetics; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D007376:Interleukin-2 / Q000235:genetics / Q000378:metabolism; D008297:Male; D020641:Polymorphism, Single Nucleotide; D018121:Receptors, Cytokine / Q000235:genetics*; D053707:Receptors, Interleukin-12 / Q000235:genetics; D012899:Smallpox / Q000208:ethnology / Q000276:immunology / Q000517:prevention & control; D012900:Smallpox Vaccine / Q000008:administration & dosage* / Q000276:immunology; D014611:Vaccination / Q000379:methods; D044465:White People / Q000235:genetics; D055815:Young Adult
chemical_list: D016207:Cytokines; C508439:IL12RB2 protein, human; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D053583:Interleukin-1beta; D007376:Interleukin-2; D018121:Receptors, Cytokine; D053707:Receptors, Interleukin-12; D012900:Smallpox Vaccine