The Journal of infectious diseases · 2011
Common SNPs/haplotypes in IL18R1 and IL18 genes are associated with variations in humoral immunity to smallpox vaccination in Caucasians and African Americans.
СтатьяПоддержка NIH: внешняя программаНазвание и аннотация: Перевод в очереди
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Haralambieva Iana H, Ovsyannikova Inna G, Dhiman Neelam, Kennedy Richard B, O'Byrne Megan, Pankratz V Shane, Jacobson Robert M, Poland Gregory A
Аннотация
BACKGROUND: Identifying genetic factors that influence poxvirus immunity across races may assist in the development of better vaccines and approaches for vaccine development.
METHODS: We performed an extensive candidate-gene genetic screen (across 32 cytokine and cytokine receptor genes) in a racially diverse cohort of 1056 healthy adults after a single dose of smallpox vaccine. Associations between single-nucleotide polymorphisms (SNPs)/haplotypes and vaccinia virus-specific neutralizing antibodies were assessed using linear regression methodologies.
RESULTS: The combined analysis identified 63 associations between candidate SNPs and antibody levels after smallpox vaccination with P < .05. Thirty-one of these were within the IL18R1 and IL18 genes. Five IL18R1 SNPs, including a coding synonymous polymorphism rs1035130 (Phe251Phe) and 2 promoter SNPs (rs6710885, rs2287037), all in linkage disequilibrium, were associated with significant variations in antibody levels in both Caucasians (P ≤ .016) and African Americans (P ≤ .025). Similarly, associations with 2 intronic IL18 SNPs (rs2043055 and rs5744280) were consistent in the Caucasian (P ≤ .023) and African American samples (P ≤ .014). Haplotype analysis revealed highly significant associations between IL18R1 haplotypes and vaccinia virus-specific antibody levels (P < .001, by combined analysis) that were consistent across races.
CONCLUSIONS: Our study provides evidence for IL18 and IL18R1 genes as plausible genes regulating the humoral immune response to smallpox vaccine in both Caucasians and African Americans.
METHODS: We performed an extensive candidate-gene genetic screen (across 32 cytokine and cytokine receptor genes) in a racially diverse cohort of 1056 healthy adults after a single dose of smallpox vaccine. Associations between single-nucleotide polymorphisms (SNPs)/haplotypes and vaccinia virus-specific neutralizing antibodies were assessed using linear regression methodologies.
RESULTS: The combined analysis identified 63 associations between candidate SNPs and antibody levels after smallpox vaccination with P < .05. Thirty-one of these were within the IL18R1 and IL18 genes. Five IL18R1 SNPs, including a coding synonymous polymorphism rs1035130 (Phe251Phe) and 2 promoter SNPs (rs6710885, rs2287037), all in linkage disequilibrium, were associated with significant variations in antibody levels in both Caucasians (P ≤ .016) and African Americans (P ≤ .025). Similarly, associations with 2 intronic IL18 SNPs (rs2043055 and rs5744280) were consistent in the Caucasian (P ≤ .023) and African American samples (P ≤ .014). Haplotype analysis revealed highly significant associations between IL18R1 haplotypes and vaccinia virus-specific antibody levels (P < .001, by combined analysis) that were consistent across races.
CONCLUSIONS: Our study provides evidence for IL18 and IL18R1 genes as plausible genes regulating the humoral immune response to smallpox vaccine in both Caucasians and African Americans.