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.

Comprehensive assessment showed no associations of variants at the SLC10A1 locus with susceptibility to persistent HBV infection among Southern Chinese

“…Of them, 1,299 and 1,067 were determined as PIs and SRs, respectively10. The male/female ratio and the mean age (s.d.)…”

Human Genetic Determinants of Viral Diseases

“…A study comparing individuals who have experienced spontaneous recovery versus chronic infection identified a novel susceptibility locus for persistent HBV at chromosome 8p21.3 (87). Expression quantitative trait loci associations from liver tissues of patients with persistent infection suggested a functional role for the INTS10 gene from this region.…”

Neutralizing Antibody Responses to Viral Infections Are Linked to the Non-classical MHC Class II Gene H2-Ob

“…Outcomes of infections with persistent viruses, such as Human Immunodeficiency Virus (HIV), Human Hepatitis C Virus (HCV) and Human Hepatitis B virus (HBV) have been linked to the Major Histocompatibility Complex (MHC). The ability to control HIV in some ‘elite controllers’ has been linked to specific MHC Class I (MHC-I) alleles (Fellay et al, 2007; Kosmrlj et al, 2010; Kulkarni et al, 2011; Miura et al, 2009; Pereyra et al, 2010) and persistence of HCV and HBV have been linked to MHC Class II (MHC-II) alleles (Chang et al, 2014; Duggal et al, 2013; Li et al, 2016). MHC involvement in virus clearance was expected since MHC-I and MHC-II genes control CD8 + T cell responses and CD4 + T cell-dependent antibody (Ab) responses, respectively.…”

“…Similarly, as spontaneous HCV clearance correlates with the early appearance of virus-neutralizing antibodies (Abs) (Osburn et al, 2014; Pestka et al, 2007) several MHC-II alleles of HLA-DQ were considered as candidates mediating efficient, CD4 + T cell-dependent humoral responses to this virus (Duggal et al, 2013). Further, the production of neutralizing Abs that play a key role in the recovery from infection with HBV (Ciupe et al, 2014; Huang et al, 2006) were also linked to specific HLA-DQ alleles (Chang et al, 2014; Li et al, 2016). …”