title: HCV F protein amplifies the predictions of IL-28B and CTLA-4 polymorphisms about the susceptibility and outcomes of HCV infection in Southeast China.
abstract: Cytotoxic T lymphocyte associated antigen-4(CTLA-4) is an inhibitory receptor with great value in the progression of hepatitis C virus (HCV) infection related diseases. To determine the potential associations of IL-28B rs12979860 and CTLA-4 rs231775, rs3087243 and rs5742909 polymorphisms with the generation of HCV F protein, susceptibility and outcomes of HCV infection, a total of 375 healthy controls, 219 HCV spontaneous recovered patients and 600 chronic HCV patients from Southeast China were recruited and genotyped in this study. And the relative mRNA levels of CTLA-4 in T cells were detected. Logistic regression analysis showed that rs231775 A allele was associated with significantly higher rate of spontaneous viral clearance in anti-HCV F antibody negative patients (adjusted OR=0.512, P=0.008), but allele A was related to higher mRNA level of CTLA-4 with the generation of HCV F protein. And rs5742909 T allele added up to the risk of HCV infection chronicity significantly in patients with the presence of HCV F protein (adjusted OR=2.698, P=0.003). Also, the rs5742909 CC genotype, along with the presence of HCV F protein, indicated a significantly higher CTLA-4 level than that in anti-HCV F antibody negative patients. The AG+AA genotype of rs3087243 significantly increased the susceptibility to HCV infection in subjects over 56 years old (adjusted OR=1.595, P=0.011). Genotype-genotype interaction between IL-28B rs12979860 and CTLA-4 rs3087243 was found to be significantly associated with increased susceptibility to HCV infection (adjusted OR=1.509, P=0.005). Haplotype analysis in CTLA-4 also showed significant association with the generation of HCV F protein. All these results indicated the importance of IL-28B and CTLA-4 polymorphisms and their associations with HCV F protein in the risk and chronicity of HCV infection in Chinese Han population in Southeast China.
authors.affiliation: School of Life Science and Technology, China Pharmaceutical University, Nanjing, China. Electronic address: xiaowen2013cpu@163.com.
authors.forename: Wen
authors.initials: W
authors.lastname: Xiao
authors.affiliation: Huadong Research Institute for Medicine and Biotechnics, Nanjing, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: School of Life Science and Technology, China Pharmaceutical University, Nanjing, China; Huadong Research Institute for Medicine and Biotechnics, Nanjing, China. Electronic address: dengxiaozhao1002@vip.sina.com.
authors.forename: Xiao Zhao
authors.initials: XZ
authors.lastname: Deng
authors.affiliation: Department of Infectious Diseases, The First Affiliated Hospital with Nanjing Medical University, Nanjing, China.
authors.forename: Long Feng
authors.initials: LF
authors.lastname: Jiang
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medicine, Nanjing Medical University, Nanjing, China.
authors.forename: Dan Yan
authors.initials: DY
authors.lastname: Zhu
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medicine, Nanjing Medical University, Nanjing, China.
authors.forename: Jia Ping
authors.initials: JP
authors.lastname: Pei
authors.affiliation: Jiangsu Food & Pharmaceutical Science College, Huaian, China.
authors.forename: Chi Yu
authors.initials: CY
authors.lastname: Ge
authors.affiliation: Huadong Research Institute for Medicine and Biotechnics, Nanjing, China.
authors.forename: Bing Jun
authors.initials: BJ
authors.lastname: Li
authors.affiliation: Huadong Research Institute for Medicine and Biotechnics, Nanjing, China. Electronic address: science2008@hotmail.com.
authors.forename: Chang Jun
authors.initials: CJ
authors.lastname: Wang
authors.affiliation: Huadong Research Institute for Medicine and Biotechnics, Nanjing, China.
authors.forename: Jing Hai
authors.initials: JH
authors.lastname: Zhang
authors.affiliation: Department of Clinical Laboratory, Nanjing Second Hospital, Nanjing, China.
authors.forename: Zhen Xian
authors.initials: ZX
authors.lastname: Zhou
authors.affiliation: Department of Clinical Laboratory, Yixing People's Hospital, Yixing, China.
authors.forename: Wei Liang
authors.initials: WL
authors.lastname: Ding
authors.affiliation: Huadong Research Institute for Medicine and Biotechnics, Nanjing, China.
authors.forename: Xiao Dong
authors.initials: XD
authors.lastname: Xu
authors.affiliation: School of Life Science and Technology, China Pharmaceutical University, Nanjing, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Yue
mesh_terms: D001483:Base Sequence; D060908:CTLA-4 Antigen / Q000235:genetics*; D016022:Case-Control Studies; D002681:China; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D016174:Hepacivirus / Q000276:immunology*; D019698:Hepatitis C, Chronic / Q000235:genetics* / Q000276:immunology / Q000628:therapy; D006801:Humans; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D016896:Treatment Outcome; D014758:Viral Core Proteins / Q000276:immunology*; D000095022:Interferon Lambda
chemical_list: D060908:CTLA-4 Antigen; D007372:Interferons; D007378:Interleukins; D014758:Viral Core Proteins; C556706:CTLA4 protein, human; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C433031:hepatitis C protein F, Hepatitis C virus
keywords: CTLA-4; Chronic HCV infection; HCV F protein; IL-28B; Polymorphism