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

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.

SUBMITTER: Li Y

PROVIDER: S-EPMC4895015 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature

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

Li Yuanfeng Y Si Lanlan L Zhai Yun Y Hu Yanling Y Hu Zhibin Z Bei Jin-Xin JX Xie Bobo B Ren Qian Q Cao Pengbo P Yang Fei F Song Qingfeng Q Bao Zhiyu Z Zhang Haitao H Han Yuqing Y Wang Zhifu Z Chen Xi X Xia Xia X Yan Hongbo H Wang Rui R Zhang Ying Y Gao Chengming C Meng Jinfeng J Tu Xinyi X Liang Xinqiang X Cui Ying Y Liu Ying Y Wu Xiaopan X Li Zhuo Z Wang Huifen H Li Zhaoxia Z Hu Bo B He Minghui M Gao Zhibo Z Xu Xiaobing X Ji Hongzan H Yu Chaohui C Sun Yi Y Xing Baocai B Yang Xiaobo X Zhang Haiying H Tan Aihua A Wu Chunlei C Jia Weihua W Li Shengping S Zeng Yi-Xin YX Shen Hongbing H He Fuchu F Mo Zengnan Z Zhang Hongxing H Zhou Gangqiao G

Nature communications 20160531

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 (ind ...[more]

PMID: 27244555

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Project description:UNLABELLED:Chinese translation BACKGROUND:Hepatitis C virus (HCV) infections occur worldwide and either spontaneously resolve or persist and markedly increase the person's lifetime risk for cirrhosis and hepatocellular carcinoma. Although HCV persistence occurs more often in persons of African ancestry and persons with genetic variants near interleukin-28B (IL-28B), the genetic basis is not well-understood. OBJECTIVE:To evaluate the host genetic basis for spontaneous resolution of HCV infection. DESIGN:2-stage, genome-wide association study. SETTING:13 international multicenter study sites. PATIENTS:919 persons with serum HCV antibodies but no HCV RNA (spontaneous resolution) and 1482 persons with serum HCV antibodies and HCV RNA (persistence). MEASUREMENTS:Frequencies of 792 721 single nucleotide polymorphisms (SNPs). RESULTS:Differences in allele frequencies between persons with spontaneous resolution and persistence were identified on chromosomes 19q13.13 and 6p21.32. On chromosome 19, allele frequency differences localized near IL-28B and included rs12979860 (overall per-allele OR, 0.45; P = 2.17 × 10-30) and 10 additional SNPs spanning 55 000 base pairs. On chromosome 6, allele frequency differences localized near genes for HLA class II and included rs4273729 (overall per-allele OR, 0.59; P = 1.71 × 10-16) near DQB1*03:01 and an additional 116 SNPs spanning 1 090 000 base pairs. The associations in chromosomes 19 and 6 were independent and additive and explain an estimated 14.9% (95% CI, 8.5% to 22.6%) and 15.8% (CI, 4.4% to 31.0%) of the variation in HCV resolution in persons of European and African ancestry, respectively. Replication of the chromosome 6 SNP, rs4272729, in an additional 745 persons confirmed the findings (P = 0.015). LIMITATION:Epigenetic effects were not studied. CONCLUSION:IL-28B and HLA class II are independently associated with spontaneous resolution of HCV infection, and SNPs marking IL-28B and DQB1*03:01 may explain approximately 15% of spontaneous resolution of HCV infection.

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

Publications

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

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