Mayo Clinic Vaccine Research Group, Mayo Clinic, Rochester, Minnesota 55905, USA.
J Infect Dis. 2010 Jan 15;201(2):207-13. doi: 10.1086/649588.
Genetic polymorphisms play an important role in rubella vaccine-induced immunity.
We genotyped 714 healthy children after 2 age-appropriate doses of rubella-containing vaccine for 142 potential single-nucleotide polymorphisms (SNPs).
Specific polymorphisms in the vitamin A receptor, retinoic acid-inducible gene I (RIG-I), and tripartite motif 5 and 22 (TRIM5 and TRIM22) genes were significantly associated with rubella vaccine humoral immunity. The minor allele of the rs4416353 in the vitamin A receptor gene was associated with an allele dose-related decrease (P = .019) in rubella antibody response. The minor allele of rs6793694, in the vitamin A receptor gene, was associated with an allele dose-related antibody decrease (p = .039). The minor variant of nonsynonymous SNP rs10813831 (Arg7Cys) in the RIG-I gene was associated with an allele dose-related decrease in rubella antibody level from 37.4 to 28.0 IU/mL (P = .035), whereas increased representation of the minor allele of the 5'UTR SNP (rs3824949, P = .015) in the antiretroviral TRIM5 gene was associated with an allele dose-related increase in rubella antibody. It is of particular interest that the nonsynonymous SNP rs3740996 (His43Tyr) in the TRIM5 gene was associated with variations in rubella antibody response (P = .016) after having been previously found to play a significant functional role.
These findings further expand our immunogenetic understanding of mechanisms of rubella vaccine-induced immunity.
遗传多态性在风疹疫苗诱导的免疫中起着重要作用。
我们对 714 名接受过两剂年龄适宜的风疹疫苗的健康儿童进行了基因分型,共检测了 142 个潜在的单核苷酸多态性(SNP)。
维生素 A 受体、视黄酸诱导基因 I(RIG-I)和三肽基 5 和 22(TRIM5 和 TRIM22)基因中的特定多态性与风疹疫苗体液免疫显著相关。维生素 A 受体基因中的 rs4416353 位点的次要等位基因与风疹抗体反应的等位基因剂量相关下降(P =.019)相关。维生素 A 受体基因中的 rs6793694 位点的次要等位基因与等位基因剂量相关的抗体下降(p =.039)相关。RIG-I 基因中的非同义 SNP rs10813831(Arg7Cys)的次要变异与风疹抗体水平的等位基因剂量相关下降相关,从 37.4 IU/mL 下降至 28.0 IU/mL(P =.035),而抗病毒 TRIM5 基因中的 5'UTR SNP(rs3824949,P =.015)的次要等位基因的增加与风疹抗体的等位基因剂量相关增加相关。特别有趣的是,TRIM5 基因中的非同义 SNP rs3740996(His43Tyr)与风疹抗体反应的变化相关(P =.016),此前发现其在功能上具有重要作用。
这些发现进一步扩展了我们对风疹疫苗诱导免疫机制的免疫遗传学理解。