Association of the OAS3 rs1859330 G/A genetic polymorphism with severity of enterovirus-71 infection in Chinese Han children
Association of the OAS3 rs1859330 G/A genetic polymorphism with severity of enterovirus-71 infection in Chinese Han children
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DOI：
10.1007/s00705-017-3381-6
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发表时间：
2017-08-01
影响因子：
2.7
通讯作者：
Chen, Zongbo
中科院分区：
文献类型：
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作者：
Tan, Yuxia;Yang, Tingting;Chen, Zongbo
2‘5’-寡腺苷合成酶(OAS)是一种干扰素诱导的蛋白，在干扰素的抗病毒作用中起着重要作用，其中OAS3是OAS1、OAS2、OAS3、OASL的四种类型之一。OAS对几种感染性病毒疾病的作用已有报道，但OAS3对肠道病毒71型(EV71)的作用缺乏研究。本研究旨在探讨OAS3基因rs1859330 G/A多态与EV71感染易感性及严重程度的关系。对370例手足口病患儿进行了调查，其中轻度214例，重度156例。采用改良的多重连接检测反应(IMLDR)技术进行基因分型。重型组的AA型分布(p=0.002)和A等位基因频率(OR=1.83，95%CI1.32~2.52，p<；0.001)均显著高于轻型组。比较EV71型感染患者的不同基因与皮疹(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)、丙氨酸氨基转移酶(p=0.02)和脑电(p=0.019)的关系。而年龄、性别、AST、CK-MB、CT/MRI及部分症状和体征(如发热天数、头痛、抽搐、意识障碍、瘫痪、脑膜刺激症状)的差异无统计学意义。重症患者脑脊液中白细胞、蛋白质、血糖、氯化物、淋巴细胞和单核细胞水平在不同基因型间无差异。EV71感染者血浆中干扰素-γ水平显著高于对照组(P<0.01)。重症患者中A等位基因携带者(AA+GA)的干扰素-γ浓度(118.5+/-12.6pg/mL)低于GG纯合子(152.6+/-56.3pg/mLp<；0.05)。提示OAS3 rs1859330 G/A基因多态性与EV-71感染的严重程度相关，A等位基因是EV71严重感染的危险因素。
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-gamma in EV71-infected patients were significantly higher than in the control group (p < 0.01). IFN-gamma 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.