Impact of cytokine and cytokine receptor gene polymorphisms on cellular immunity after smallpox vaccination |
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Authors: | Inna G Ovsyannikova Iana H Haralambieva Richard B Kennedy V Shane Pankratz Robert A Vierkant Robert M Jacobson Gregory A Poland |
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Institution: | 1. Mayo Clinic Vaccine Research Group, Mayo Clinic, Rochester, MN 55905, USA;2. Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, MN 55905, USA;3. Department of Health Sciences Research, Mayo Clinic, Rochester, MN 55905, USA;4. Program in Translational Immunovirology and Biodefense, Mayo Clinic, Rochester, MN 55905, USA |
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Abstract: | We explored associations between SNPs in cytokine/cytokine receptor genes and cellular immunity in subjects following primary smallpox vaccination. We also analyzed the genotype–phenotype associations discovered in the Caucasian subjects among a cohort of African-Americans. In Caucasians we found 277 associations (p < 0.05) between gene SNPs and inter-individual variations in IFN-α, IL-12p40, IL-1β, IL-2, and TNF-α secretion levels. A collection of SNPs in the IL1RN, IL2RB, IL4R, IL6, IL10RB, IL12A, and IL12RB2 genes had consistent associations among both Caucasians and African-Americans. A regulatory SNP (rs452204) in the IL1RN gene was significantly associated with higher levels of IL-2 secretion in an allele dose-dependent manner in both race groups (p = 0.05 for Caucasians and p = 0.002 for African-Americans). IL12RB2 polymorphism rs3790567 was associated with a dose-related decrease in IL-1β secretion (p = 0.009 for Caucasians and p = 0.01 for African-Americans). Our results demonstrate that variations in smallpox vaccine-induced cytokine responses are modulated by genetic polymorphisms in cytokine and cytokine receptor genes. |
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Keywords: | SNPs single-nucleotide polymorphisms HLA human leukocyte antigen IL interleukin HWE Hardy&ndash Weinberg equilibrium IQR inter-quartile range |
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