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Genome-wide analysis of polymorphisms associated with cytokine responses in smallpox vaccine recipients

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Abstract

The role that genetics play in response to infection or disease is becoming increasingly clear as we learn more about immunogenetics and host–pathogen interactions. Here we report a genome-wide analysis of the effects of host genetic variation on cytokine responses to vaccinia virus stimulation in smallpox vaccine recipients. Our data show that vaccinia stimulation of immune individuals results in secretion of inflammatory and Th1 cytokines. We identified multiple SNPs significantly associated with variations in cytokine secretion. These SNPs are found in genes with known immune function, as well as in genes encoding for proteins involved in signal transduction, cytoskeleton, membrane channels and ion transport, as well as others with no previously identified connection to immune responses. The large number of significant SNP associations implies that cytokine secretion in response to vaccinia virus is a complex process controlled by multiple genes and gene families. Follow-up studies to replicate these findings and then pursue mechanistic studies will provide a greater understanding of how genetic variation influences vaccine responses.

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Acknowledgments

We extend our thanks to Drs. Meg Ryan and Kevin L. Russell, the Naval Health Research Center team, and the Mayo Vaccine Research Group nurses and study coordinators for their efforts in subject recruitment. We thank Julie M. Cunningham and the Mayo Advanced Genomic Technology Center for genotyping efforts, as well as Megan O’Byrne and David Watson for assistance with the statistical analysis. Funding support was provided by the National Institute of Allergies and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, Contract No. HHSN266200400065C. The contents of this manuscript are solely the responsibility of the authors and do not necessarily represent the official views of the National Institute of Allergy and Infectious Diseases or the National Institutes of Health.

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The authors do not have any conflicts of interest to report.

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All experiments described here comply with the current, applicable US laws.

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Authors and Affiliations

  1. Mayo Vaccine Research Group, Mayo Clinic, Guggenheim 611C, 200 First Street SW, Rochester, MN, 55905, USA

    Richard B. Kennedy, Inna G. Ovsyannikova, Iana H. Haralambieva & Gregory A. Poland

  2. Program in Translational Immunovirology and Biodefense, Mayo Clinic, Rochester, MN, USA

    Richard B. Kennedy, Inna G. Ovsyannikova, Iana H. Haralambieva & Gregory A. Poland

  3. Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, USA

    V. Shane Pankratz & Robert A. Vierkant

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  1. Richard B. Kennedy
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  2. Inna G. Ovsyannikova
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Correspondence to Gregory A. Poland.

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Kennedy, R.B., Ovsyannikova, I.G., Shane Pankratz, V. et al. Genome-wide analysis of polymorphisms associated with cytokine responses in smallpox vaccine recipients. Hum Genet 131, 1403–1421 (2012). https://doi.org/10.1007/s00439-012-1174-2

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