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Correlation Analysis Between CDHR3 Locus Rs6967330 And Disease Severity Of Hospitalized Children With Lower Respiratory Tract Infection Caused By Rhinovirus

Posted on:2020-03-10Degree:MasterType:Thesis
Country:ChinaCandidate:H LiFull Text:PDF
GTID:2404330590980341Subject:Academy of Pediatrics
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PART ? CORRELATION ANALYSIS BETWEEN CDHR3 LOCUS RS6967330 AND DISEASE SEVERITY OF HOSPITALIZED CHILDREN WITH LOWER RESPIRATORY TRACT INFECTION CAUSED BY RHINOVIRUSBackground and objective: Human rhinovirus(HRV)is not only the most common cause of the cold but is also associated with hospitalization of acute lower respiratory tract infection in infants and young children.The cadherin-associated family member 3(CDHR3)is the newly discovered rhinovirus C receptor,and the single nucleotide polymorphism(SNP)site rs6967330 of the human CDHR3 gene is associated with asthma and HRV infection.This study was to explore the association of single nucleotide polymorphism at rs6967330 of CDHR3 gene with HRV viral load and acute lower respiratory tract infection caused by HRV in children.Methods: From January,2012 to November,2014,we collected specimens of nasopharyngeal aspirates from children with acute lower respiratory tract infection caused by HRVs.CDHR3 gene fragment was amplified by PCR from the samples and sequenced for rs6967330 genotyping.The VP4 gene of HRV was amplified with PCR for subsequent sequencing,and real-time fluorescent quantitative PCR was used to estimate the virus load.The correlation between rs6967330 genotypes and HRV viral load and the clinical features of the children was analyzed.Results: Of the 200 children with acute lower respiratory tract infection caused by HRVs,30(15.0%)had AA/AG genotype and 170(85.0%)had GG genotype of rs6967330.The children with AA/AG genotype were more likely to have wheezing symptoms than those with GG genotype(86.7% vs.57.1%,P=0.002),and were also more susceptible to severe pneumonia(30.0% vs.11.2%,P=0.018);the first-degree relatives of the children with AA/AG genotype were also more likely to have a history of atopic disease(16.7% vs.5.9%,P=0.039).Logistic regression analysis revealed that rs6967330 A was a risk factor for wheezing in children with HRV infection(OR: 4.585,95% CI: 1.446 ~ 14.541,P=0.010)and also for progression into severe cases(OR: 3.379,95% CI: 1.009 ~ 11.315,P=0.048).No significant differences in HRV subtypes or viral loads were found between the children with different genotypes of rs6967330.Conclusion: The SNP of CDHR3 gene at rs6967330 may beassociated with severe cases and wheezing after lower respiratory tract infection with HRV in children.PART ? MOLECULAR EPIDEMIOLOGICAL STUDY OF HUMAN ENTEROVIRUS D68 IN HOSPITALIZED CHILDREN WITH RESPIRATORY INFECTION IN CHONGQINGBackground and objective: The human enterovirus D68 belongs to the genus Enterovirus,a family of picornaviruses that can cause respiratory diseases.This study was to observe the prevalence of HEV-D68 in hospitalized children with respiratory infection in Chongqing and to analyze the clinical features and gene sequence characteristics of HEV-D68 isolates in Chongqing.Methods: From January,2012 to December,2018,we collected specimens of nasopharyngeal aspirates from hospitalized children with respiratory infections in the Respiratory Center of Children's Hospital of Chongqing Medical University.Multiple PCR methods were used to detect common respiratory viruses.VP1 gene were amplified and sequenced in the HEV-D68 detected positive specimens.The clinical features of HEV-D68 detected patients were further analyzed.Results: Of the 2857 NPA specimens,20 were positive for HEV-D68(0.7%,20/2857),mainly detected in 2016(18 cases,90.0%).Compared with 2014 HEV-D68-positive children,the 2016 children in Chongqing were younger(48.9±31.8 vs.26.8±24.5,P=0.037)and had a longer course(10.1 ± 5.2 vs.17.4 ± 11.2 P=0.036)and more cases with a family atopic history(15.4% vs.55.6%,P=0.032).VP1 gene sequencing revealed that the 218 th amino acid of HEV-D68 was S in 2014 and the mutation was T/A in 2016.Conclusion: The 218 th amino acid of HEV-D68 VP1 in 2016 has been mutated and may be more susceptible to small age children.
Keywords/Search Tags:CDHR3 gene, single nucleotide polymorphism, rhinovirus, Human enterovirus D68, respiratory infection, amino acid mutation
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