Genetic mutations in NF-kappa B pathway genes were associated with the protection from hepatitis C virus infection among Chinese Han population
Genetic mutations in NF-kappa B pathway genes were associated with the protection from hepatitis C virus infection among Chinese Han population
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NF-kappa B 通路基因的基因突变与中国汉族人群丙型肝炎病毒感染的保护作用相关
DOI：
10.1038/s41598-019-47058-y
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发表时间：
2019
影响因子：
4.6
通讯作者：
Huang Peng
中科院分区：
文献类型：
--
作者：
Yue Ming;Tian Ting;Wang Chunhui;Fan Haozhi;Wu Jingjing;Wang Jinke;Li Jun;Xia Xueshan;Zhang Amei;Yu Rongbin;Zhang Yun;Huang Peng
宿主基因多态性是导致HCV感染的主要因素之一。NF-κB蛋白在免疫应答中起着多种作用，并参与HCV的感染和进展。本研究旨在探讨NF-κB B通路单核苷酸多态性（SNPs）与HCV感染易感性及转归的关系。共纳入1642例中国受试者，其中963例为未感染者，231例为病毒自发清除者，448例为HCV持续感染者，采用TaqMan方法检测其中4个SNP（Rel rs 842647，NF-κB2 rs 12769316，RelA rs7101916，RelB rs 28372683）。使用在线生物信息学工具分析潜在的功能多态性。Logistic回归分析结果显示，RelA rs7101916 T等位基因（PBonferroni= 0.016）和RelB rs 28372683 A等位基因（PBonferroni= 4.8e-5）与中国汉族人群HCV感染易感性降低相关，与累积效应和单倍型分析结果一致。对SNPs功能的计算机分析表明，rs7101916和rs 28372683位点的遗传变异可影响基因的转录调控和表达，进而影响NF-κB通路的激活和HCV感染的易感性。本研究首次报道了RelA rs7101916 T或RelB rs 28372683 A的携带是中国人群抗HCV感染的潜在保护因素。
Host genetic polymorphism is one of major unalterable major factors for HCV infection. NF-κB proteins play multiple roles in immune response and involve in HCV infection and progression. This study was conducted to explore the relationship between single nucleotide polymorphisms (SNPs) in NF-κB pathway and the susceptibility as well as resolution of HCV infection. A total of 1642 Chinese subjects were enrolled in the study, including 963 uninfected control cases, 231 cases with spontaneous viral clearance and 448 cases with persistent HCV infection, and four SNPs (Rel rs842647, NF-κB2 rs12769316, RelA rs7101916, RelB rs28372683) were genotyped by TaqMan assay among them. Potentially functional polymorphisms were analyzed using online bioinformatics tools. The logistic analyses results indicated that RelA rs7101916 T allele (PBonferroni= 0.016) and RelB rs28372683 A allele (PBonferroni= 4.8e-5) were associated with an decreased risk of the susceptibility to HCV infection among Chinese Han population, which were consistent with the results of cumulative effects and haplotype analysis. Thesilicoanalysis of SNPs function suggested that the genetic variation of rs7101916 and rs28372683 could influence gene transcriptional regulation and expression, subsequently affecting NF-κB pathway activation and the susceptibility to HCV infection. This study firstly reported that the carriage of RelA rs7101916 T or RelB rs28372683 A was the potential protective factor against HCV infection among the Chinese population.