Tan Yuxia, Yang Tingting, Liu Peipei, Chen Liping, Tian Qingwu, Guo Ya, He Hongfang, Liu Yedan, Chen Zongbo
Department of Pediatrics, The Affiliated Hospital of Qingdao University, No. 59, Haier Road, Qingdao, 266000, China.
Department of Pediatrics, Zibo City Maternal and Child Health Hospital, Zibo, 255029, Shandong, China.
Arch Virol. 2017 Aug;162(8):2305-2313. doi: 10.1007/s00705-017-3381-6. Epub 2017 Apr 25.
The 2'5'-oligoadenylate synthetase (OAS) is an interferon (IFN)-induced protein that plays an important role in the antiviral action of IFN, with OAS3 being one of the four OAS classes (OAS1, OAS2, OAS3, OASL). The effect of OAS on several infectious viral diseases has been reported; however, a study of the effect of OAS3 on enterovirus 71 (EV71) is lacking. The purpose of this study was to evaluate the association of the OAS3 rs1859330 G/A genetic polymorphism with susceptibility and severity of EV71 infection. We investigated 370 Chinese Han children with hand-foot-mouth disease (HFMD) (214 of which were mild cases while 156 were severe). An improved multiplex ligation detection reaction (iMLDR) technique was carried out to examine the genotype. The AA genotype distribution (p = 0.002) and A allele frequency (OR = 1.83, 95% CI 1.32-2.52, p < 0.001) of OAS3 rs1859330 in severe cases were significantly higher than in mild cases. When comparing the different genotypes in EV71-infected patients, there were statistical differences in relation to rash (p = 0.03), oral ulcers (p = 0.005), pathologic reflex (p = 0.003), WBC counts (p = 0.032), CRP (p = 0.024), BG concentrations (p = 0.029), ALT (p = 0.02), and EEG (p = 0.019). However, there were no differences in relation to age, gender, AST, CK-MB, CT/ MRI, as well as some symptoms and signs (e.g. duration of fever (days), headache, convulsions, consciousness disturbance, paralysis, sign of meningeal irritation). In the cerebrospinal fluid (CSF) of severe cases, there were no differences in the levels of white cells, protein, glucose, chloride, lymphocytes and monocytes between the different genotypes. The plasma levels of IFN-γ in EV71-infected patients were significantly higher than in the control group (p < 0.01). IFN-γ concentrations in severe cases were lower in A allele carriers (AA+GA) (118.5 ± 12.6pg/mL) than in GG homozygotes (152.6 ± 56.3pg/mL p < 0.05). These findings suggest that the OAS3 rs1859330 G/A genetic polymorphism is associated with the severity of EV-71 infection, and that the A allele is a risk factor for the development of severe EV71 infection.
2',5'-寡腺苷酸合成酶（OAS）是一种干扰素（IFN）诱导蛋白，在IFN的抗病毒作用中发挥重要作用，OAS3是OAS的四个类别之一（OAS1、OAS2、OAS3、OASL）。已有报道OAS对多种传染性病毒疾病的影响；然而，缺乏关于OAS3对肠道病毒71型（EV71）影响的研究。本研究的目的是评估OAS3 rs1859330 G/A基因多态性与EV71感染易感性及严重程度的关联。我们调查了370名中国汉族手足口病（HFMD）儿童（其中214例为轻症病例，156例为重症病例）。采用改进的多重连接检测反应（iMLDR）技术检测基因型。重症病例中OAS3 rs1859330的AA基因型分布（p = 0.002）和A等位基因频率（OR = 1.83，95%CI 1.32 - 2.52，p < 0.001）显著高于轻症病例。比较EV71感染患者的不同基因型时，在皮疹（p = 0.03）、口腔溃疡（p = 0.005）、病理反射（p = 0.003）、白细胞计数（p = 0.032）、C反应蛋白（p = 0.024）、血糖浓度（p = 0.029）、谷丙转氨酶（p = 0.02）和脑电图（p = 0.019）方面存在统计学差异。然而，在年龄、性别、谷草转氨酶、肌酸激酶同工酶、CT/磁共振成像以及一些症状和体征（如发热天数、头痛、惊厥、意识障碍、瘫痪、脑膜刺激征）方面没有差异。在重症病例的脑脊液（CSF）中，不同基因型之间白细胞、蛋白质、葡萄糖、氯化物、淋巴细胞和单核细胞水平没有差异。EV71感染患者的血浆干扰素-γ水平显著高于对照组（p < 0.01）。A等位基因携带者（AA + GA）的重症病例中干扰素-γ浓度（118.5 ± 12.6pg/mL）低于GG纯合子（152.6 ± 56.3pg/mL，p < 0.05）。这些发现表明，OAS3 rs1859330 G/A基因多态性与EV - 71感染的严重程度相关，且A等位基因是重症EV71感染发生的危险因素。
