期刊
NATURE COMMUNICATIONS
卷 7, 期 -, 页码 -出版社
NATURE PORTFOLIO
DOI: 10.1038/ncomms11664
关键词
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资金
- National Natural Science Foundation of China [81125017, 81222027]
- Chinese National Programs for Fundamental Research and Development [2013CB910301]
- Program of Beijing Municipal Commission for Science and Technology for Frontier Technology of Life Science [Z141100000214014]
- Chinese National Programs for High Technology Research and Development [2012AA02A205, 2012AA020204, 2012AA022002]
- Chinese Key Project for Infectious Diseases [2013ZX10002009]
- International ST Cooperation [2014DFB30020]
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.
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