Genome-wide association study identifies 8p21.3 associated with persistent hepatitis B virus infection among Chinese
Genome-wide association study identifies 8p21.3 associated with persistent hepatitis B virus infection among Chinese
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DOI：
10.1038/ncomms11664
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发表时间：
2016-05-01
影响因子：
16.6
通讯作者：
Zhou, Gangqiao
中科院分区：
文献类型：
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作者：
Li, Yuanfeng;Si, Lanlan;Zhou, Gangqiao
乙型肝炎病毒（HBV）感染是一种常见的传染病。在此，我们在中国人群中进行了一项全基因组关联研究（GWAS），以确定与持续性HBV感染相关的新基因位点。在1251名持续性HBV感染个体（持续性感染者，病例组）和1057名自然康复个体（自然康复者，对照组）中进行了GWAS扫描，随后在总共由3905名持续性感染者和3356名自然康复者组成的四个独立人群中进行了重复验证。我们在8p21.3处确定了一个新的位点（索引rs7000921，优势比 = 0.78，P = 3.2×10⁻¹²）。此外，我们确定了8p21.3处INTS10基因显著的表达数量性状位点关联。我们证明INTS10通过干扰素调节因子3（IRF3）在肝细胞中抑制HBV复制。在临床血浆样本中，我们证实与自然康复者相比，持续性感染者中INTS10水平显著降低，且与HBV载量呈负相关。这些发现凸显了8p21.3处一个在HBV感染清除中起作用的新的抗病毒基因INTS10。
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 x 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.