Genome-wide association study identifies 8p21.3 associated with persistent hepatitis B virus infection among Chinese

作者：Yuanfeng Li, Lanlan Si, Yun Zhai, Yanling Hu, Zhibin Hu, Jin‐Xin Bei, Bobo Xie, Qian Ren, Pengbo Cao, Fei Yang, Qingfeng Song, Zhiyu Bao, Hai‐Tao Zhang, Yuqing Han, Yuqing Han, Zhifu Wang, Xi Chen, Xia Xia, Hongbo Yan, Rui Wang, Ying Zhang, Chengming Gao, Jinfeng Meng, Xinyi Tu, Xinqiang Liang, Ying Liu, Ying Liu, Xiaopan Wu, Zhuo Li, Huifen Wang, Zhaoxia Li, Minghui He, Minghui He, Zhibo Gao, Xiaobing Xu, 季洪赞, Chaohui Yu, Yi Sun, Baocai Xing, Xiaobo Yang, Haiying Zhang, Haiying Zhang, Aihua Tan, Chunlei Wu, Weihua Jia, Shengping Li, Yi-Xin Zeng, Hongbing Shen, Fuchu He, Zengnan Mo, Hongxing Zhang, Hongxing Zhang, Gangqiao Zhou · 发表于：Nature Communications · 年份：2016 · DOI：10.1038/ncomms11664 · 被引用次数：72 · 研究领域：Hepatitis B Virus Studies、Liver Disease Diagnosis and Treatment、Hepatitis C virus research

Hepatitis B virus (HBV) infection is a common infectious disease. Here we perform a genome-wide association study (GWAS) among Chinese populations to identify novel genetic loci involved in persistent HBV infection. GWAS scan is performed in 1,251 persistently HBV infected subjects (PIs, cases) and 1,057 spontaneously recovered subjects (SRs, controls), followed by replications in four independent populations totally consisting of 3,905 PIs and 3,356 SRs. We identify a novel locus at 8p21.3 (index rs7000921, odds ratio=0.78, P=3.2 × 10(-12)). Furthermore, we identify significant expression quantitative trait locus associations for INTS10 gene at 8p21.3. We demonstrate that INST10 suppresses HBV replication via IRF3 in liver cells. In clinical plasma samples, we confirm that INST10 levels are significantly decreased in PIs compared with SRs, and negatively correlated with the HBV load. These findings highlight a novel antiviral gene INTS10 at 8p21.3 in the clearance of HBV infection.