TY - JOUR
T1 - Variations in measles vaccine-specific humoral immunity by polymorphisms in SLAM and CD46 measles virus receptors
AU - Dhiman, Neelam
AU - Poland, Gregory A.
AU - Cunningham, Julie M.
AU - Jacobson, Robert M.
AU - Ovsyannikova, Inna G.
AU - Vierkant, Robert A.
AU - Wu, Yanhong
AU - Pankratz, V. Shane
N1 - Funding Information:
Disclosure of potential conflict of interest: G. A. Poland has consulting arrangements with and has received grant support from Merck. R. M. Jacobson has received grant support from Merck. The rest of the authors have declared that they have no conflict of interest.
Funding Information:
Supported by a Mayo Clinic and Foundation grant (MIDAS) and in part by National Institutes of Health grants AI 33144 and AI 48793 and General Clinical Research Center (GCRC) grant M01-RR00585.
PY - 2007/9
Y1 - 2007/9
N2 - Background: Measles infection requires 2 cellular receptors, signaling lymphocyte activation molecule (SLAM) and CD46. Known and novel single nucleotide polymorphisms (SNPs) in SLAM and CD46 genes might influence the immune response to measles vaccine. Objective: We sought to identify SNP associations in SLAM and CD46 genes with variations in measles antibody response. Methods: We genotyped known SNPs in SLAM and CD46 genes in 339 subjects vaccinated with 2 doses of measles-mumps-rubella vaccine. We also sequenced the measles virus-binding domains of SLAM and CD46 to identify novel SNPs. Results: Increased representation of minor alleles for rs3796504 and rs164288 in the SLAM gene was associated with an allele dose-related decrease (4-fold) in measles-specific antibodies. Heterozygous genotype TC for rs12076998 located in the untranslated region 33 bp upstream of the measles virus-binding domain of the SLAM gene was associated with higher median antibody levels (1991 vs 1467 IU/L, P = .01) compared with wild-type TT. Within the CD46 gene, the minor allele C for intronic SNP (rs11118580) was associated with an allele dose-related decrease in measles antibodies (1072 vs 1795 IU/L, P < .01). Decreases in minor allele counts for rs3796504, rs164288, and rs1118580 demonstrated a significant (P < .001) additive effect on measles-specific antibodies. Conclusion: Our data suggest that specific SNPs present in both the SLAM and CD46 genes are associated with measurable and significant variations in antibody response after measles vaccination. Clinical implications: Understanding the immunogenetics of measles vaccine receptors is important to better understand variations in immune responses to vaccines and to design better vaccines.
AB - Background: Measles infection requires 2 cellular receptors, signaling lymphocyte activation molecule (SLAM) and CD46. Known and novel single nucleotide polymorphisms (SNPs) in SLAM and CD46 genes might influence the immune response to measles vaccine. Objective: We sought to identify SNP associations in SLAM and CD46 genes with variations in measles antibody response. Methods: We genotyped known SNPs in SLAM and CD46 genes in 339 subjects vaccinated with 2 doses of measles-mumps-rubella vaccine. We also sequenced the measles virus-binding domains of SLAM and CD46 to identify novel SNPs. Results: Increased representation of minor alleles for rs3796504 and rs164288 in the SLAM gene was associated with an allele dose-related decrease (4-fold) in measles-specific antibodies. Heterozygous genotype TC for rs12076998 located in the untranslated region 33 bp upstream of the measles virus-binding domain of the SLAM gene was associated with higher median antibody levels (1991 vs 1467 IU/L, P = .01) compared with wild-type TT. Within the CD46 gene, the minor allele C for intronic SNP (rs11118580) was associated with an allele dose-related decrease in measles antibodies (1072 vs 1795 IU/L, P < .01). Decreases in minor allele counts for rs3796504, rs164288, and rs1118580 demonstrated a significant (P < .001) additive effect on measles-specific antibodies. Conclusion: Our data suggest that specific SNPs present in both the SLAM and CD46 genes are associated with measurable and significant variations in antibody response after measles vaccination. Clinical implications: Understanding the immunogenetics of measles vaccine receptors is important to better understand variations in immune responses to vaccines and to design better vaccines.
KW - CD46
KW - Measles vaccine
KW - measles virus receptors
KW - signaling lymphocyte activation molecule
KW - single nucleotide polymorphisms
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U2 - 10.1016/j.jaci.2007.04.036
DO - 10.1016/j.jaci.2007.04.036
M3 - Article
C2 - 17560639
AN - SCOPUS:34548290878
SN - 0091-6749
VL - 120
SP - 666
EP - 672
JO - Journal of Allergy and Clinical Immunology
JF - Journal of Allergy and Clinical Immunology
IS - 3
ER -