title: The relevance of Tim-3 polymorphisms and F protein to the outcomes of HCV infection.
abstract: Hepatitis C virus (HCV) is one of the major causes of liver inflammation. The aim of this study was to investigate the associations of T-cell immunoglobulin and mucin domain-3 (Tim-3) polymorphisms and the alternate reading frame protein (F protein) with the outcomes of HCV infection. Three single-nucleotide polymorphisms (SNPs; rs10053538, rs12186731, and rs13170556) of Tim-3 were genotyped in this study, which included 203 healthy controls, 558 hepatitis C anti-F-positive patients, and 163 hepatitis C anti-F-negative patients. The results revealed that the rs12186731 CT and rs13170556 TC and CC genotypes were significantly less frequent in the anti-F-positive patients [odds ratio (OR) = 0.54, 95 % confidence interval (CI) = 0.35-0.83, p = 0.005; OR = 0.26, 95 % CI = 0.18-0.39, p < 0.001; and OR = 0.19, 95 % CI = 0.10-0.35, p < 0.001, respectively), and the rs13170556 TC genotype was more frequent in the chronic HCV (CHC) patients (OR = 1.70, 95 % CI = 1.20-2.40, p = 0.002). The combined analysis of the rs12186731 CT and rs13170556 TC/CC genotypes revealed a locus-dosage protective effect in the anti-F-positive patients (OR = 0.22, 95 % CI = 0.14-0.33, p trend < 0.001). Stratified analyses revealed that the frequencies of the rs12186731 (CT + TT) genotypes were significantly lower in the older (OR = 0.31, 95 % CI = 0.15-0.65, p = 0.002) and female (OR = 0.30, 95 % CI = 0.17-0.52, p < 0.001) subgroups, and rs13170556 (TC + CC) genotypes exhibited the same effect in all subgroups (all p < 0.001) in the anti-F antibody generations. Moreover, the rs13170556 (TC + CC) genotypes were significantly more frequent in the younger (OR = 1.86, 95 % CI = 1.18-2.94, p = 0.007) and female (OR = 2.38, 95 % CI = 1.48-3.83, p < 0.001) subgroups of CHC patients. These findings suggest that the rs12186731 CT and rs13170556 TC/CC genotypes of Tim-3 provide potential protective effects with the F protein in the outcomes of HCV infection and that these effects are related to sex and age.
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medicine, Nanjing Medical University, Nanjing, 210029, China.
authors.forename: J P
authors.initials: JP
authors.lastname: Pei
authors.affiliation: Department of Infectious Diseases, The First Affiliated Hospital with Nanjing Medical University, Nanjing, 210002, China.
authors.forename: L F
authors.initials: LF
authors.lastname: Jiang
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medicine, Nanjing Medical University, Nanjing, 210029, China.
authors.forename: X W
authors.initials: XW
authors.lastname: Ji
authors.affiliation: School of Life Science and Technology, China Pharmaceutical University, Nanjing, 210009, China. xiaowen2013cpu@163.com.
authors.forename: W
authors.initials: W
authors.lastname: Xiao
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medicine, Nanjing Medical University, Nanjing, 210029, China. dengxiaozhao1002@vip.sina.com.|Huadong Research Institute for Medicine and Biotechnics, No. 293, Zhongshan East Road, Nanjing, 210002, China. dengxiaozhao1002@vip.sina.com.
authors.forename: X Z
authors.initials: XZ
authors.lastname: Deng
authors.affiliation: Department of Clinical Laboratory, Nanjing Second Hospital, Nanjing, China.
authors.forename: Z X
authors.initials: ZX
authors.lastname: Zhou
authors.affiliation: Department of Infectious Diseases at Luoyang Central Hospital Affiliated to Zhengzhou University, Luoyang, 471000, China.
authors.forename: D Y
authors.initials: DY
authors.lastname: Zhu
authors.affiliation: Department of Clinical Laboratory, Yixing People's Hospital, Yixing, 214200, China.
authors.forename: W L
authors.initials: WL
authors.lastname: Ding
authors.affiliation: Huadong Research Institute for Medicine and Biotechnics, No. 293, Zhongshan East Road, Nanjing, 210002, China.
authors.forename: J H
authors.initials: JH
authors.lastname: Zhang
authors.affiliation: Huadong Research Institute for Medicine and Biotechnics, No. 293, Zhongshan East Road, Nanjing, 210002, China.
authors.forename: C J
authors.initials: CJ
authors.lastname: Wang
authors.affiliation: Faculty of Chemical Engineering, Huaiyin Institute of Technology, Meicheng Road East, Huai'an, 223003, China.
authors.forename: K
authors.initials: K
authors.lastname: Jing
mesh_terms: D000328:Adult; D000914:Antibodies, Viral / Q000097:blood; D005260:Female; D000072597:Hepatitis A Virus Cellular Receptor 2 / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000188:drug therapy / Q000453:epidemiology* / Q000235:genetics* / Q000276:immunology; D054884:Host-Pathogen Interactions / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D014758:Viral Core Proteins / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; C448908:HAVCR2 protein, human; D000072597:Hepatitis A Virus Cellular Receptor 2; D014758:Viral Core Proteins; C433031:hepatitis C protein F, Hepatitis C virus