Genetic basis for adverse events after smallpox vaccination

Abstract

Identifying genetic factors associated with the development of adverse events might allow screening before vaccinia virus administration. Two independent clinical trials of the smallpox vaccine (Aventis Pasteur) were conducted in healthy, vaccinia virus-naive adult volunteers. Volunteers were assessed repeatedly for local and systemic adverse events (AEs) associated with the receipt of vaccine and underwent genotyping for 1442 single-nucleotide polymorphisms (SNPs). In the first study, 36 SNPs in 26 genes were associated with systemic AEs (P ≤ .05); these 26 genes were tested in the second study. In the final analysis, 3 SNPs were consistently associated with AEs in both studies. The presence of a nonsynonymous SNP in the methylenetetrahydrofolate reductase (MTHFR) gene was associated with the risk of AE in both trials (odds ratio [OR], 2.3 [95% confidence interval {CI}, 1.1-5.2] [P = .04] and OR, 4.1 [95% CI, 1.4 -11.4] [P