TLR3-1377C/T基因多态性及表达水平与儿童肠道病毒71型脑炎易感性的探讨

Association of TLR3-1377C/T gene polymorphisms and expression with susceptibility to enterovirus 71 encephalitis in children

摘要:

目的 研究Toll样受体（TLRs）基因TLR3-1377C/T位点基因多态性及TLR3表达水平与儿童肠道病毒71型（EV71）脑炎易感性之间的关系。方法 收集EV71感染患儿187例（脑炎组59例和无脑炎组128例）与同期健康体检儿童232例进行病例对照研究。采用聚合酶链反应限制性片段长度多态性（PCR-RFLP）方法对TLR3-1377C/T基因多态性进行检测，采用ELISA检测血清TLR3水平。结果 与EV71感染无脑炎组相比，脑炎组TLR3-1377C/T位点基因型分布及等位基因频率的差异无统计学意义（P > 0.05）。与对照组相比，EV71感染脑炎组、无脑炎组的血清TLR3水平均显著增高（P < 0.05），以无脑炎组最高（P < 0.05）。脑炎组的EV71病毒载量高于无脑炎组（P < 0.01）。< 1岁或 ≥ 1岁的EV71感染脑炎组、无脑炎组患儿的血清TLR3水平均较相应对照组增高（P < 0.05），其中无脑炎组TLR3水平高于相应年龄的脑炎组（P < 0.05）。脑炎组≥1岁患儿的TLR3浓度高于< 1岁者（P < 0.05）；无脑炎组及对照组的TLR3浓度在< 1岁或≥1岁患儿之间的差异无统计学意义（P > 0.05）。EV71感染脑炎组，< 1岁患儿所占比例高于 ≥ 1岁者（P < 0.05）。结论 TLR3-1377C/T位点的基因多态性与EV71脑炎的发生无明显相关性。TLR3的低表达可能导致对病毒复制的抑制作用减弱，促进了EV71脑炎的发生。婴儿EV71感染后血清TLR3的表达不足可能是其合并脑炎的重要因素。

Abstract:

Objective To investigate the association of gene polymorphisms of Toll-like receptor 3 (TLR3)-1377C/T and expression of TLR3 with the susceptibility to enterovirus 71 (EV71) encephalitis in children. Methods A total of 187 children with EV71 infection (59 children in the encephalitis group and 128 in the non-encephalitis group) and 232 children who underwent physical examination were enrolled in the case-control study. Polymerase chain reaction-restriction fragment length polymorphism was used to detect the TLR3-1377C/T gene polymorphisms. ELISA was used to measure the serum level of TLR3. Results There were no significant differences in the genotype and allele frequencies of TLR3-1377C/T between the non-encephalitis group and the encephalitis group. Compared with the control group, the encephalitis group and the non-encephalitis group had significant increases in the serum level of TLR3 (P < 0.05), and the non-encephalitis group had the highest level (P < 0.05). The encephalitis group had a significantly higher EV71 viral load than the non-encephalitis group (P < 0.01). The children aged < 1 year or ≥ 1 year in the encephalitis group and the non-encephalitis group had significant increases in the serum level of TLR3 compared with their counterparts in the control group (P < 0.05), and the children aged < 1 year or ≥ 1 year in the non-encephalitis group had a significantly higher serum level of TLR3 than those in the encephalitis group (P < 0.05). In the encephalitis group, the children aged ≥ 1 year had a significantly higher TLR3 concentration than those aged < 1 year (P < 0.05), and there were no significant differences in the TLR3 concentration between the children aged ≥ 1 year and < 1 year in the non-encephalitis group and the control group. In the encephalitis group, the proportion of children aged < 1 year was significantly higher than those aged ≥ 1 year (P < 0.05). Conclusions The TLR3-1377C/T gene polymorphisms are not significantly associated with the development of EV71 encephalitis. Low expression of TLR3 might weaken the inhibitory effect on virus replication and promote the development of EV71 encephalitis. The deficiency in the expression of TLR3 in serum after EV71 infection might be an important factor for the development of encephalitis in infants.