Pei J P, Jiang L F, Ji X W, Xiao W, Deng X Z, Zhou Z X, Zhu D Y, Ding W L, Zhang J H, Wang C J, Jing K
Department of Biochemistry and Molecular Biology, School of Basic Medicine, Nanjing Medical University, Nanjing, 210029, China.
Department of Infectious Diseases, The First Affiliated Hospital with Nanjing Medical University, Nanjing, 210002, China.
Eur J Clin Microbiol Infect Dis. 2016 Aug;35(8):1377-86. doi: 10.1007/s10096-016-2676-y. Epub 2016 May 26.
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.
丙型肝炎病毒（HCV）是肝脏炎症的主要病因之一。本研究旨在探讨T细胞免疫球蛋白和粘蛋白结构域3（Tim-3）基因多态性以及交替阅读框蛋白（F蛋白）与HCV感染结局之间的关联。本研究对Tim-3的三个单核苷酸多态性（SNP；rs10053538、rs12186731和rs13170556）进行了基因分型，研究对象包括203名健康对照者、558名抗F阳性丙型肝炎患者和163名抗F阴性丙型肝炎患者。结果显示，抗F阳性患者中rs12186731 CT、rs13170556 TC和CC基因型的频率显著较低[比值比（OR）=0.54，95%置信区间（CI）=0.35 - 0.83，p = 0.005；OR = 0.26，95% CI = 0.18 - 0.39，p < 0.001；OR = 0.19，95% CI = 0.10 - 0.35，p < 0.001]，并且rs13170556 TC基因型在慢性HCV（CHC）患者中更为常见（OR = 1.70，95% CI = 1.20 - 2.40，p = 0.002）。rs12186731 CT和rs13170556 TC/CC基因型的联合分析显示，在抗F阳性患者中存在基因座剂量保护效应（OR = 0.22，95% CI = 0.14 - 0.33，p趋势< 0.001）。分层分析显示，rs12186731（CT + TT）基因型在年龄较大（OR = 0.31，95% CI = 0.15 - 0.65，p = 0.002）和女性（OR = 0.30，95% CI = 0.17 - 0.52，p < 0.001）亚组中的频率显著较低，并且rs13170556（TC + CC）基因型在抗F抗体产生的所有亚组中均表现出相同的效应（所有p < 0.001）。此外，rs13170556（TC + CC）基因型在CHC患者的年龄较小（OR = 1.86，95% CI = 1.18 - 2.94，p = 0.007）和女性（OR = 2.38，95% CI = 1.48 - 3.83，p < 0.001）亚组中更为常见。这些发现表明，Tim-3的rs12186731 CT和rs13170556 TC/CC基因型在HCV感染结局中与F蛋白一起提供了潜在的保护作用，并且这些作用与性别和年龄有关。
