Common SNPs/haplotypes in IL18R1 and IL18 genes are associated with variations in humoral immunity to smallpox vaccination in Caucasians and African Americans - PubMed (original) (raw)

Common SNPs/haplotypes in IL18R1 and IL18 genes are associated with variations in humoral immunity to smallpox vaccination in Caucasians and African Americans

Iana H Haralambieva et al. J Infect Dis. 2011.

Abstract

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.

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Figures

Figure 1.

Figure 1.

Haplotype block structure of the IL18R1 single-nucleotide polymorphisms (SNPs) with consistent associations among racial groups in the study cohort. The linkage disequilibrium block structure was analyzed using Haploview software, version 3.32. The _r_2 color scheme is as follows: white (_r_2=0), shades of gray (0< _r_2 <1), black (_r_2 = 1). The numbers report the D' statistic multiplied by 100. Analysis was performed on all Caucasians (A) and all African Americans (B) separately because of variations in allele frequencies across populations.

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