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Nat Commun. 2016 May 31;7:11664. doi: 10.1038/ncomms11664.

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

Li Y1,2,3, Si L1,2,3, Zhai Y1,2,3, Hu Y4, Hu Z5, Bei JX6, Xie B1,2,3, Ren Q1,2,3, Cao P1,2,3, Yang F1,2,3, Song Q7, Bao Z7, Zhang H1,2,3, Han Y1,2,3, Wang Z1,2,3, Chen X1,2,3, Xia X1,2,3, Yan H1,2,3, Wang R1,2,3, Zhang Y1,2,3, Gao C1,2,3, Meng J1,2,3, Tu X1,2,3, Liang X7, Cui Y7, Liu Y8, Wu X8, Li Z9, Wang H10, Li Z11, Hu B11, He M12, Gao Z12, Xu X13, Ji H13, Yu C14, Sun Y15, Xing B15, Yang X4, Zhang H4, Tan A4, Wu C4, Jia W6, Li S6, Zeng YX6, Shen H5, He F1,2,3, Mo Z4, Zhang H1,2,3, Zhou G1,2,3.

Author information

1
State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing 100850, China.
2
National Engineering Research Center for Protein Drugs, Beijing 100850, China.
3
National Center for Protein Sciences at Beijing, Beijing 100850, China.
4
Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi 530021, China.
5
Department of Epidemiology and Biostatistics, MOE Key Laboratory of Modern Toxicology, School of Public Health, Nanjing Medical University, Nanjing 210029, China.
6
State Key Laboratory of Oncology in Southern China, Guangzhou 510060, China.
7
Affiliated Cancer Hospital of Guangxi Medical University, Nanning, Guangxi 530021, China.
8
National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing 100005, China.
9
Department of Infectious Disease, Affiliated You'an Hospital, Capital University of Medical Science, Beijing 100069, China.
10
Liver Failure Treatment and Research Center, Beijing 302 Hospital, Beijing 100039, China.
11
Department of Clinical Laboratory, the Third Affiliated Hospital, Sun Yat-sen University, Guangzhou 510630, China.
12
BGI-Shenzhen, Shenzhen 518031, China.
13
Department of Gastroenterology and Hepatology, Jinling Hospital, Clinical School of Nanjing University, Nanjing 210002, China.
14
Department of Gastroenterology, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310006, China.
15
Department of Hepatobiliary Surgery I, Peking University Cancer Hospital and Institute, Beijing 100142, China.

Abstract

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.

PMID:
27244555
PMCID:
PMC4895015
DOI:
10.1038/ncomms11664
[Indexed for MEDLINE]
Free PMC Article

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