OAS1基因SNP对儿童手足口病易感性和疾病严重性的影响及临床意义

The effect and clinical significance of OAS1 gene SNP for the severity and susceptibility in children with hand,foot and mouth disease

目的探讨OAS1基因单核苷酸多态性(SNP)对儿童手足口病(HFMD)易感性和疾病严重程度的影响及其临床意义,为HFMD的防治提供依据。方法收集2014年12月至2019年12月我院住院治疗的340例儿童HFMD患儿,其中重症HFMD患儿141例,轻型HFMD 199例,另外以120例健康体检儿童作为正常对照组,采集外周静脉血,提取基因组DNA,采用聚合酶链反应-限制性片段长度多态性技术检测OAS1 rsl0774671和rs2660单核苷酸多态位点的分布情况,并用凝胶电泳和测序进行验证,分析各个基因位点多态性与HFMD易感性、严重程度的相关关系。结果OAS1 rs10774671 GG基因型和G等位基因频率在CA16组中明显高于正常对照组(P=0.000),轻症HFMD OAS1 rs10774671位点GG基因型频率显著高于重症HFMD(P=0.032);OAS1 rs10774671位点GG基因型分布男童显著多于女童(P=0.011)。OAS1 rs2660 AG基因型和G等位基因频率在EV71组中明显高于正常对照组(P=0.001),重症HFMD OAS1rs2660位点AG基因型频率显著高于轻症HFMD(P=0.004);携带OAS1基因rs10774671、rs2660 GG基因型的患儿均比AA基因型和AG基因型的患儿IFN-γ水平明显升高(P=0.05),携带rs2660 GG基因型的IFN-γ水平较携带rs10774671 GG基因型也明显升高(P=0.017)。结论OAS1 rs10774671位点GG基因型儿童更易感染CA16,与轻症HFMD相关;OAS1 rs2660位点AG基因型儿童更易感染EV71,与重症HFMD相关;IFN-γ可能参与了HFMD的免疫发病。

Objective To explore the effect and clinical significance of 2’-5’oligoadenylates synthesis1(OAS1)gene SNP for the severity and susceptibility in children with hand,foot and mouth disease(HFMD),and to provide a basis for the prevention and treatment of HFMD.Methods A total of 340 children hospitalized in our hospital from December 2014 to December 2019 were selected,including 141 with severe HFMD,199 with mild HFMD,and 120 healthy children as the control group.Collect peripheral venous blood,extract genomic DNA,and use polymerase chain reaction-restriction fragment length polymorphism to detect the distribution of OAS1 rsl0774671 and rs2660 single nucleotide polymorphisms,and verify by gel electrophoresis and sequencing.Analyze the correlation between the polymorphism of each gene locus and the susceptibility and severity of HFMD.Results The frequencies of OAS1 rs10774671 GG genotype and G allele in CA16 group were significantly higher in HFMD than that in control group(P=0.000).The frequency of OAS1 rs10774671 GG genotype in mild HFMD was significantly higher than that in severe HFMD(P=0.032);The OAS1 rs10774671 GG genotype distribution in boys was significantly higher than that in girls(P=0.011).The frequencies of OAS1 rs2660 GG genotype and G allele in EV71group were significantly higher than that in control group(P=0.001).The frequency of OAS1 rs2660 AG genotype in severe HFMD was significantly higher than that in mild HFMD(P=0.004).The expression level of IFN-γin patients carried with OAS1 rs10774671 and rs2660 GG genotypes was significantly higher than that with AA and AG genotypes(P=0.05),The expression level of IFN-γin patients carried with rs2660 GG genotype was also significantly higher than that with rs10774671 GG genotype(P=0.017).Conclusion Children who carried with OAS1 rs10774671 GG genotypes were more susceptible to CA16 infection,which were associated with mild HFMD;Children who carried with OAS1 rs2660 AG genotypes were more susceptible to EV71 infection,which were associated with severe HFMD;IFN-γmay be involved in the immune pathogenesis of HFMD.