Dhiman Neelam, Poland Gregory A, Cunningham Julie M, Jacobson Robert M, Ovsyannikova Inna G, Vierkant Robert A, Wu Yanhong, Pankratz V Shane
Mayo Vaccine Research Group, Mayo Clinic, Rochester, Minn, USA.
J Allergy Clin Immunol. 2007 Sep;120(3):666-72. doi: 10.1016/j.jaci.2007.04.036. Epub 2007 Jun 8.
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.
We sought to identify SNP associations in SLAM and CD46 genes with variations in measles antibody response.
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.
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.
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.
Understanding the immunogenetics of measles vaccine receptors is important to better understand variations in immune responses to vaccines and to design better vaccines.
麻疹感染需要两种细胞受体，即信号淋巴细胞激活分子（SLAM）和CD46。SLAM和CD46基因中已知的和新发现的单核苷酸多态性（SNP）可能会影响对麻疹疫苗的免疫反应。
我们试图确定SLAM和CD46基因中的SNP与麻疹抗体反应变化之间的关联。
我们对339名接种两剂麻疹-腮腺炎-风疹疫苗的受试者的SLAM和CD46基因中的已知SNP进行了基因分型。我们还对SLAM和CD46的麻疹病毒结合域进行了测序，以确定新的SNP。
SLAM基因中rs3796504和rs164288的次要等位基因频率增加与麻疹特异性抗体呈等位基因剂量相关的降低（4倍）有关。位于SLAM基因麻疹病毒结合域上游33 bp非翻译区的rs12076998的杂合基因型TC与野生型TT相比，具有更高的抗体水平中位数（1991对1467 IU/L，P = 0.01）。在CD46基因中，内含子SNP（rs11118580）的次要等位基因C与麻疹抗体呈等位基因剂量相关的降低（1072对1795 IU/L，P < 0.01）有关。rs3796504、rs164288和rs1118580的次要等位基因计数减少对麻疹特异性抗体具有显著的（P < 0.001）累加效应。
我们的数据表明，SLAM和CD46基因中存在的特定SNP与麻疹疫苗接种后抗体反应的可测量和显著变化有关。
了解麻疹疫苗受体的免疫遗传学对于更好地理解疫苗免疫反应的变化以及设计更好的疫苗非常重要。
