| Objective: Enterovirus 71(EV71)is one of the enteroviruses belonging to picornaviruses.Compared with other enteroviruses,EV71 has the obvious feature of neurotropic.In recent years,hand,foot and mouth disease caused by EV71 has spread in various regions of the Asia-Pacific region,especially in mainland China.The high disability rate and mortality caused by severe infection of EV71 lead to a heavy social burden.So it is an effective means of early prevention to identify the risk factors of EV71 severe infection.The severity of EV71 encephalitis is associated not only with viral virulence but also with the genetic susceptibility of the host.Previous studies showed that EV71 encephalitis is associated with interleukin 18(IL-18)gene polymorphism.The aim of this study was to investigate whether IL-18 gene-607C/A site(rs1946519)is associated with EV71 infection encephalitis or not,and compared the serum IFN-? concentrations among each genotype in patients with EV71 encephalitis.Method: 195 patients with EV71 infection were collected from the Affiliated Hospital of Qingdao University and Qingdao Women and Children's Hospital from May 2014 to June 2016.A total of 214 children undergoing a health check-up in hospital were gathered as the control group in the same period.We collected the EDTA anticoagulant samples,were performed by reverse transcription-polymerse chain reaction detection(RT-PCR)to detect EV71.The result of laboratory examinations,physical examination,and collection of fecal and EDTA anticoagulant samples were performed by reverse transcription-polymerase chain reactin detection(RT-PCR)to detect EV71.According to the clinical manifestations and laboratory test results of the children,they were divided into 92 cases of nonencephalitis and 93 cases of encephalitis group including 49 cases of severe encephalitis.The clinical features and auxiliary examination results were collected and compared in cases.The polymorphism of IL-18-607C/A was detected by modified multiplex ligase technology(i MLDR),and the concentration level of IFN-? in serum was detected by enzyme-linked immunosorbent assays(ELISA).Statistical data were processed by SPSS 21.0 software.The t-test was used to compare the quantitative data sets of the two groups with normal distribution.The comparison between the two groups of normal distribution quantitative data was analyzed by Analysis of Variance(ANOVA).?2test was used to compare qualitative data groups.Pearson's collection Statistical analysis was performed using Statistical Package for Social Science(IBM SPSS software,U.S.A.)with a released version 21.0 and significance was set at a P-value <0.05.Result: 1.We analyzed the polymorphisms in IL-18-607C/A gene of 185 EV71 infected patients and 214 controls for genetic association research.The frequency of IL-18-607 AA genotype and IL-18-607 A allele in EV71 infected patients was significantly higher than in controls(32.4% vs 21.5%,P=0.042,55.1% vs 46.0%,P=0.001).2.The genotype and allele frequency of IL-18-607C/A gene were not significantly different between EV71 encephalitis group and non-encephalitis group(P1 = 0.292,P2 = 0.119,OR = 1.386,95% CI = 0.919-2.090).3.The frequency of AA genotype was significantly increased in the severe encephalitis group(P1 = 0.003)compared with encephalitis,and the A allele was also significantly increased(P2 = 0.016,OR = 2.063,95% CI = 1.139-3.736).The risk of developing EV71 severe encephalitis increased by 2.063 times when the child carried the A allele.4.Among different genotypes of EV71 infection,C-reactive protein(CRP),white blood cell count,fever duration,blood glucose levels were significantly different.There were no significant differences in gender,age,alanine aminotransferase(ALT),aspartate aminotransferase(AST),and creatine kinase isoenzyme(CK-MB).There were no significant differences in other clinical manifestations such as vomiting,seizures,mental changes,maximum body temperature,brain magnetic resonance(MRI),and EEG.5.The serum concentration of IFN-? was obviously higher in the severe EV71 encephalitis than in the mild and control group.Meanwhile,the serum concentration of IFN-? in the encephalitis group with AA genotype was significantly lower than that in the CC genotype.Conclusion: 1.Patients with IL-18-607 AA genotype have obvious susceptibility to EV71 infection.2.The IL-18-607 gene polymorphism may not be associated with susceptibility to EV71 encephalitis.3.In EV71-infected encephalitis,children with the IL-18-607 AA genotype may be more likely to progress to severe encephalitis. |
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