title: A functional polymorphism in IFNAR1 gene is associated with susceptibility and severity of HFMD with EV71 infection.
abstract: Enterovirus 71 (EV71), one of the major pathogens of Hand, foot and mouth disease (HFMD), results in millions of infections and hundreds of deaths each year in Southeast Asia. Biased infection and variable clinical manifestations of EV71 HFMD indicated that host genetic background played an important role in the occurrence and development of the disease. We identified the mRNA profiles of EV71 HFMD patients, which type I interferon (IFN) pathway related genes were down-regulated. Four single nucleotide polymorphisms (SNPs) of type I IFN receptor 1 (IFNAR1) were chosen to analyze their relationships to EV71 infection. We found that genotype GG of promoter variant rs2843710 was associated with the susceptibility and severity to EV71 HFMD. In addition, we assessed the regulatory effects of rs2843710 to IFN stimulated genes (ISGs), and found that the expressions of IFNAR1, OAS1 and MX1 were significantly lower in patients with rs2843710 genotype GG. And rs2843710 allele G showed weaker transcriptional activity compared with allele C. Our study indicated that rs2843710 of IFNAR1 was associated with the susceptibility and severity of EV71 HFMD in Chinese Han populations, acting as a functional polymorphism by regulating ISGs expression, such as OAS1 and MX1.
authors.affiliation: Department of Infectious Diseases, Shenzhen Third People's Hospital, University of South China, Shenzhen, 518112, China.|Guangdong Key Laboratory of Infectious Diseases, Shenzhen Third People's Hospital, Guangdong Medical College, Shenzhen, 518112, China.
authors.forename: Rongrong
authors.initials: R
authors.lastname: Zou
authors.affiliation: Guangdong Key Laboratory of Infectious Diseases, Shenzhen Third People's Hospital, Guangdong Medical College, Shenzhen, 518112, China.|Shenzhen Key Laboratory of Pathogen and Immunity, Shenzhen Third People's Hospital, Shenzhen, 518112, China.
authors.forename: Guoliang
authors.initials: G
authors.lastname: Zhang
authors.affiliation: Guangdong Key Laboratory of Infectious Diseases, Shenzhen Third People's Hospital, Guangdong Medical College, Shenzhen, 518112, China.
authors.forename: Shaoyuan
authors.initials: S
authors.lastname: Li
authors.affiliation: Guangdong Key Laboratory of Infectious Diseases, Shenzhen Third People's Hospital, Guangdong Medical College, Shenzhen, 518112, China.
authors.forename: Wenfei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Guangdong Key Laboratory of Infectious Diseases, Shenzhen Third People's Hospital, Guangdong Medical College, Shenzhen, 518112, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Yuan
authors.affiliation: Guangdong Key Laboratory of Infectious Diseases, Shenzhen Third People's Hospital, Guangdong Medical College, Shenzhen, 518112, China.
authors.forename: Jianming
authors.initials: J
authors.lastname: Li
authors.affiliation: Guangdong Key Laboratory of Infectious Diseases, Shenzhen Third People's Hospital, Guangdong Medical College, Shenzhen, 518112, China.
authors.forename: Yanrong
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Guangdong Key Laboratory of Infectious Diseases, Shenzhen Third People's Hospital, Guangdong Medical College, Shenzhen, 518112, China.
authors.forename: Yimin
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Department of Infectious Diseases, Shenzhen Third People's Hospital, University of South China, Shenzhen, 518112, China.|Guangdong Key Laboratory of Infectious Diseases, Shenzhen Third People's Hospital, Guangdong Medical College, Shenzhen, 518112, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Deng
authors.affiliation: Guangdong Key Laboratory of Infectious Diseases, Shenzhen Third People's Hospital, Guangdong Medical College, Shenzhen, 518112, China.
authors.forename: Boping
authors.initials: B
authors.lastname: Zhou
authors.affiliation: Shenzhen Key Laboratory of Pathogen and Immunity, Shenzhen Third People's Hospital, Shenzhen, 518112, China.|Center for Molecular Virology, CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, 100101, Beijing.
authors.forename: George Fu
authors.initials: GF
authors.lastname: Gao
authors.affiliation: Department of Infectious Diseases, Shenzhen Third People's Hospital, University of South China, Shenzhen, 518112, China.|Guangdong Key Laboratory of Infectious Diseases, Shenzhen Third People's Hospital, Guangdong Medical College, Shenzhen, 518112, China.|Shenzhen Key Laboratory of Pathogen and Immunity, Shenzhen Third People's Hospital, Shenzhen, 518112, China.
authors.forename: Yingxia
authors.initials: Y
authors.lastname: Liu
mesh_terms: D015088:2',5'-Oligoadenylate Synthetase / Q000235:genetics / Q000378:metabolism; D000483:Alleles; D002675:Child, Preschool; D002681:China; D029821:Enterovirus A, Human / Q000502:physiology*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006232:Hand, Foot and Mouth Disease / Q000235:genetics* / Q000473:pathology* / Q000821:virology; D006801:Humans; D007223:Infant; D007963:Leukocytes, Mononuclear / Q000378:metabolism / Q000821:virology; D008297:Male; D064547:Myxovirus Resistance Proteins / Q000235:genetics / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D053633:Receptor, Interferon alpha-beta / Q000235:genetics* / Q000378:metabolism; D012720:Severity of Illness Index; D059467:Transcriptome
chemical_list: C507964:IFNAR1 protein, human; C579071:MX1 protein, human; D064547:Myxovirus Resistance Proteins; D053633:Receptor, Interferon alpha-beta; C475085:OAS1 protein, human; D015088:2',5'-Oligoadenylate Synthetase