4.7 Article Proceedings Paper

Associations between measles vaccine immunity and single-nucleotide polymorphisms in cytokine and cytokine receptor genes

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JOURNAL OF INFECTIOUS DISEASES
卷 195, 期 1, 页码 21-29

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OXFORD UNIV PRESS INC
DOI: 10.1086/510596

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  1. NATIONAL CENTER FOR RESEARCH RESOURCES [M01RR000585] Funding Source: NIH RePORTER
  2. NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [R37AI048793, R01AI048793] Funding Source: NIH RePORTER
  3. NCRR NIH HHS [M01-RR00585] Funding Source: Medline
  4. NIAID NIH HHS [AI 33144, AI 48793] Funding Source: Medline

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Background. Cytokines are key regulators of measles vaccine humoral and cellular immunity. Single-nucleotide polymorphisms (SNPs) that are associated with differences in cytokine levels should also influence measles vaccine induced immunity. Methods. We genotyped 118 measles-mumps-rubella-vaccinated subjects for SNPs from 6 cytokine genes (interleukin [IL]-2, IL-4, IL-10, IL-12A, IL-12B, and interferon [IFN]-gamma) and their receptors (IL-2RA, IL-2RB, IL-4RA, IL-10RA, IL-10RB, IL-12RB1, IL-12RB2, and IFN-gamma R). Associations of SNPs with measles-specific antibodies, lymphoproliferation, and secreted cytokines were determined using chi(2) tests and analyses of covariance. Results. We found significant associations (P < .05) between SNPs in the IL-2, IL-10, and IL-12RB genes and measles vaccine-induced immunity. The IVS1-100G (rs2069762) and the Ex2-34G (rs2069763) SNPs within the IL-2 gene were associated with high antibody and high lymphoproliferative responses, whereas SNPs within the IL-10 and IL-12R genes were associated with low antibody and lymphoproliferative responses to measles. SNPs within the IL-4RA and IL-12B genes varied significantly (P < .05) across immune response measures. Significant associations were also found between SNPs and secreted cytokine levels. Conclusions. Specific SNPs in the cytokine and cytokine receptor genes are significantly associated with variations in measures of the immune response to measles vaccination. These results need to be further validated in a larger cohort.

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