title: Genome-wide analysis of polymorphisms associated with cytokine responses in smallpox vaccine recipients.
abstract: The role that genetics play in response to infection or disease is becoming increasingly clear as we learn more about immunogenetics and host-pathogen interactions. Here we report a genome-wide analysis of the effects of host genetic variation on cytokine responses to vaccinia virus stimulation in smallpox vaccine recipients. Our data show that vaccinia stimulation of immune individuals results in secretion of inflammatory and Th1 cytokines. We identified multiple SNPs significantly associated with variations in cytokine secretion. These SNPs are found in genes with known immune function, as well as in genes encoding for proteins involved in signal transduction, cytoskeleton, membrane channels and ion transport, as well as others with no previously identified connection to immune responses. The large number of significant SNP associations implies that cytokine secretion in response to vaccinia virus is a complex process controlled by multiple genes and gene families. Follow-up studies to replicate these findings and then pursue mechanistic studies will provide a greater understanding of how genetic variation influences vaccine responses.
authors.affiliation: Mayo Vaccine Research Group, Mayo Clinic, Guggenheim 611C, Rochester, MN 55905, USA.
authors.forename: Richard B
authors.initials: RB
authors.lastname: Kennedy
authors.forename: Inna G
authors.initials: IG
authors.lastname: Ovsyannikova
authors.forename: V Shane
authors.initials: VS
authors.lastname: Pankratz
authors.forename: Iana H
authors.initials: IH
authors.lastname: Haralambieva
authors.forename: Robert A
authors.initials: RA
authors.lastname: Vierkant
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Poland
mesh_terms: D016207:Cytokines / Q000096:biosynthesis*; D004797:Enzyme-Linked Immunosorbent Assay; D055106:Genome-Wide Association Study; D006801:Humans; D007111:Immunity, Cellular; D020641:Polymorphism, Single Nucleotide; D012900:Smallpox Vaccine / Q000008:administration & dosage* / Q000276:immunology
chemical_list: D016207:Cytokines; D012900:Smallpox Vaccine