期刊
JOURNAL OF INFECTIOUS DISEASES
卷 198, 期 1, 页码 16-22出版社
OXFORD UNIV PRESS INC
DOI: 10.1086/588670
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资金
- NCRR NIH HHS [M01 RR-00095] Funding Source: Medline
- NIAID NIH HHS [R21 AI059365, R01 AI059694, K25 AI064625, R21-AI-59365, N01-AI-25462, R01-AI-59694, N01AI25462, K25-AI-64625, R01 AI059694-05] Funding Source: Medline
- NIGMS NIH HHS [R01 GM-62758, T32 GM062758] Funding Source: Medline
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<. 01]). Two SNPs in the interferon regulatory factor-1 (IRF1) gene were associated with the risk of AE in both sample sets (OR, 3.2 [95% CI, 1.1-9.8] [P = .03] and OR, 3.0 [95% CI, 1.1-8.3] [P = .03]). Genetic polymorphisms in genes expressing an enzyme previously associated with adverse reactions to a variety of pharmacologic agents (MTHFR) and an immunological transcription factor (IRF1) were associated with AEs after smallpox vaccination in 2 independent study samples.
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