Huang Xubo, Glessner Joseph T, Huang Jinxia, Zhou Desheng, March Michael E, Wang Hongna, Xia Qianghua, Hakonarson Hakon, Li Jin
Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, China.
Key Laboratory for Cell Homeostasis and Cancer Research of Guangdong Higher Education Institutes, Guangzhou Medical University, Guangzhou, China.
Front Cell Dev Biol. 2021 Aug 12;9:690882. doi: 10.3389/fcell.2021.690882. eCollection 2021.
Hepatitis is an inflammatory condition of the liver, which is frequently caused by the infection of hepatitis B virus (HBV) or hepatitis C virus (HCV). Hepatitis can lead to the development of chronic complications including cancer, making it a major public health burden. Co-infection of HBV and HCV can result in faster disease progression. Therefore, it is important to identify shared genetic susceptibility loci for HBV and HCV infection to further understand the underlying mechanism. Through a meta-analysis based on genome-wide association summary statistics of HBV and HCV infection, we found one novel locus in the Asian population and two novel loci in the European population. By functional annotation based on multi-omics data, we identified the likely target genes at each novel locus, such as and , which play a critical role in autophagy and immune response to virus. By re-analyzing a microarray dataset from Hmgb1 mice and RNA-seq data from mouse liver tissue overexpressing , we found that differential expression of autophagy and immune and metabolic gene pathways underlie these conditions. Our study reveals novel common susceptibility loci to HBV and HCV infection, supporting their role in linking autophagy signaling and immune response.
肝炎是肝脏的一种炎症性疾病，通常由乙型肝炎病毒（HBV）或丙型肝炎病毒（HCV）感染引起。肝炎可导致包括癌症在内的慢性并发症的发生，使其成为一项重大的公共卫生负担。HBV和HCV的合并感染可导致疾病进展更快。因此，识别HBV和HCV感染的共同遗传易感性位点对于进一步了解潜在机制很重要。通过基于HBV和HCV感染的全基因组关联汇总统计数据的荟萃分析，我们在亚洲人群中发现了一个新位点，在欧洲人群中发现了两个新位点。通过基于多组学数据的功能注释，我们确定了每个新位点可能的靶基因，如 和 ，它们在自噬和对病毒的免疫反应中起关键作用。通过重新分析来自Hmgb1小鼠的微阵列数据集和过表达 的小鼠肝脏组织的RNA测序数据，我们发现自噬以及免疫和代谢基因途径的差异表达是这些情况的基础。我们的研究揭示了HBV和HCV感染新的共同易感性位点，支持了它们在连接自噬信号传导和免疫反应中的作用。
