He Hongfang, Liu Shihai, Liu Pei-Pei, Li Qiu-Bo, Tan Yu-Xia, Guo Ya, Li Fei, Wang Yuan-Yuan, Liu Ye-Dan, Yang Cheng-Qing, Chen Zong-Bo
Pediatric Department of the Affiliated Hospital of Qingdao University Medical School, No. 16 Jiangsu Road, Qingdao, 266003, Shandong, People's Republic of China.
Medical Research Center, The Affiliated Hospital of Qingdao University Medical School, Qingdao, People's Republic of China.
Arch Virol. 2017 Jun;162(6):1717-1723. doi: 10.1007/s00705-017-3265-9. Epub 2017 Feb 11.
Enterovirus 71 (EV71) infection has become one of the major threats to children globally in recent years. Toll-like receptor 3 (TLR3) plays an essential role in host defense against EV71 infection. This study was designed to assess the possible association between the TLR3c.1377C/T polymorphism and disease severity in Chinese children with EV71 infection. The TLR3c.1377C/T gene polymorphism was identified in EV71-infected patients (n = 177), including mild cases (n = 99) and severe cases (n = 78) as well as healthy controls (n = 225), using improved multiplex ligation detection reaction (iMLDR) technology. Serum levels of IFN-γ and IL-4 were measured using enzyme-linked immunosorbent assays. The presence of the TT genotype (p = 0.030) and the T allele (OR, 1.8; 95% CI, 1.2-2.8; p = 0.010) was significantly more frequent in severe cases. The plasma levels of IFN-γ and the IFN-γ/IL-4 ratio were significantly lower with the TT (102.0 ± 24.2 pg/mL, p < 0.01 and 14.2 ± 2.8, p < 0.001) and CT genotypes (114.1 ± 26.2 pg/mL, p < 0.05 and 18.0 ± 3.1, p < 0.001) than with the CC genotype (135.5 ± 36.8 pg/mL and 24.9 ± 4.7), but the plasma levels of IL-4 with the TT (7.3 ± 1.7 pg/mL, p < 0.01) and CT genotypes (6.4 ± 1.3 pg/mL, p < 0.05) were significantly higher than with the CC genotype (5.5 ±1.3 pg/mL). These findings suggest that the TLR3c.1377T allele is associated with susceptibility to severe EV71 infection in Chinese children.
近年来，肠道病毒71型（EV71）感染已成为全球儿童面临的主要威胁之一。Toll样受体3（TLR3）在宿主抵御EV71感染中发挥着重要作用。本研究旨在评估TLR3基因c.1377C/T多态性与中国EV71感染儿童疾病严重程度之间的可能关联。采用改良多重连接检测反应（iMLDR）技术，对177例EV71感染患者（包括99例轻症患者和78例重症患者）以及225例健康对照者进行了TLR3基因c.1377C/T多态性鉴定。采用酶联免疫吸附测定法检测血清中IFN-γ和IL-4水平。重症病例中TT基因型（p = 0.030）和T等位基因（OR，1.8；95%CI，1.2 - 2.8；p = 0.010）的出现频率显著更高。与CC基因型（135.5±36.8 pg/mL和24.9±4.7）相比，TT基因型（102.0±24.2 pg/mL，p < 0.01和14.2±2.8，p < 0.001）和CT基因型（114.1±26.2 pg/mL，p < 0.05和18.0±3.1，p < 0.001）的血浆IFN-γ水平及IFN-γ/IL-4比值显著降低，但TT基因型（7.3±1.7 pg/mL，p < 0.01）和CT基因型（6.4±1.3 pg/mL，p < 0.05）的血浆IL-4水平显著高于CC基因型（5.5±1.3 pg/mL）。这些发现表明，TLR3基因c.1377T等位基因与中国儿童严重EV71感染的易感性相关。
