TY - JOUR
T1 - Associations between SNPs in toll-like receptors and related intracellular signaling molecules and immune responses to measles vaccine
T2 - Preliminary results
AU - Dhiman, Neelam
AU - Ovsyannikova, Inna G.
AU - Vierkant, Robert A.
AU - Ryan, Jenna E.
AU - Shane Pankratz, V.
AU - Jacobson, Robert M.
AU - Poland, Gregory A.
N1 - Funding Information:
This work was supported by NIH grants AI 33144, AI 48793 and was made possible by Grant Number 1 UL1 RR024150-01 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH), and the NIH Roadmap for Medical Research. Its contents are solely the responsibility of the authors and do not necessarily represent the official view of NCRR or NIH. Information on NCRR is available at http://www.ncrr.nih.gov/ . Information on Reengineering the Clinical Research Enterprise can be obtained from http://nihroadmap.nih.gov/clinicalresearch/overviewtranslational.asp .
PY - 2008/3/25
Y1 - 2008/3/25
N2 - Toll-like receptors (TLRs) represent the critical "bridge" between innate and adaptive immunity to viral pathogens. We hypothesized that single nucleotide polymorphisms (SNPs) that potentially influence the expression/function of TLRs and their associated intracellular signaling molecules contribute to variations in humoral and cellular immunity to measles vaccine. We genotyped 190 randomly selected subjects (12-18 years old), previously vaccinated with two doses of measles, for known SNPs in TLR 2, 3, 4, 5, 6, 7, 8 and 9, and their associated intracellular signaling genes. Specific SNPs in the TLR 2, 3, 4, 5, 6, MyD88 and MD2 genes were associated with measles-specific humoral and cellular immunity. Heterozygous variants for rs3775291 (Phe412Leu) and rs5743305 (-926 bp in promoter region) of the TLR3 gene were associated with low antibody and lymphoproliferative responses (p ≤ 0.02) to measles vaccination. Heterozygous variants for rs4986790 (Gly299Asp) and rs4986791 (Ile399Thr) in the TLR4 gene demonstrated higher levels of (p ≤ 0.02) IL-4 secretion. Heterozygous variants for SNPs in TLR5 (rs5744174) and TLR6 (rs5743818) were associated with higher levels of (p ≤ 0.02) IFN-γ secretion. In addition, SNPs in MyD88 and MD2, intracellular molecules that associate with TLRs, also demonstrated associations with variations in antibody and IL-10 production (p ≤ 0.03). Thus, we identified specific SNP associations between TLRs and their associated signaling molecules that have a known role in viral immunity and variations in both humoral and cellular immunity following measles vaccination. These data contribute to understanding the immunogenetic mechanisms underlying variations in the immune response to measles vaccine.
AB - Toll-like receptors (TLRs) represent the critical "bridge" between innate and adaptive immunity to viral pathogens. We hypothesized that single nucleotide polymorphisms (SNPs) that potentially influence the expression/function of TLRs and their associated intracellular signaling molecules contribute to variations in humoral and cellular immunity to measles vaccine. We genotyped 190 randomly selected subjects (12-18 years old), previously vaccinated with two doses of measles, for known SNPs in TLR 2, 3, 4, 5, 6, 7, 8 and 9, and their associated intracellular signaling genes. Specific SNPs in the TLR 2, 3, 4, 5, 6, MyD88 and MD2 genes were associated with measles-specific humoral and cellular immunity. Heterozygous variants for rs3775291 (Phe412Leu) and rs5743305 (-926 bp in promoter region) of the TLR3 gene were associated with low antibody and lymphoproliferative responses (p ≤ 0.02) to measles vaccination. Heterozygous variants for rs4986790 (Gly299Asp) and rs4986791 (Ile399Thr) in the TLR4 gene demonstrated higher levels of (p ≤ 0.02) IL-4 secretion. Heterozygous variants for SNPs in TLR5 (rs5744174) and TLR6 (rs5743818) were associated with higher levels of (p ≤ 0.02) IFN-γ secretion. In addition, SNPs in MyD88 and MD2, intracellular molecules that associate with TLRs, also demonstrated associations with variations in antibody and IL-10 production (p ≤ 0.03). Thus, we identified specific SNP associations between TLRs and their associated signaling molecules that have a known role in viral immunity and variations in both humoral and cellular immunity following measles vaccination. These data contribute to understanding the immunogenetic mechanisms underlying variations in the immune response to measles vaccine.
KW - Cytokines
KW - Measles
KW - Polymorphisms
KW - Toll-like receptors
KW - Vaccine
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U2 - 10.1016/j.vaccine.2008.01.017
DO - 10.1016/j.vaccine.2008.01.017
M3 - Article
C2 - 18325643
AN - SCOPUS:40649086623
SN - 0264-410X
VL - 26
SP - 1731
EP - 1736
JO - Vaccine
JF - Vaccine
IS - 14
ER -