Biology Faculty Articles

Document Type

Article

Publication Date

1-13-2021

Publication Title

BMC Medical Genomics

Keywords

HBV infection, disease progression, GWAS, Host genetic factors, SNPs

ISSN

1755-8794

Abstract

Background: Recent studies have identified susceptibility genes of HBV clearance, chronic hepatitis B, liver cirrhosis, hepatocellular carcinoma, and showed the host genetic factors play an important role in these HBV-related outcomes.

Results: In order to discover new susceptibility genes for HBV-related outcomes, we conducted a genome-wide association study in 1031 Chinese participants, including 275 HBV clearance subjects, 92 asymptomatic persistence infection carriers (ASPI), 93 chronic hepatitis B patients (CHB), 188 HBV-related decompensated cirrhosis patients (DC), 214 HBV-related hepatocellular carcinoma patients (HCC) and 169 healthy controls (HC). In the case-control study, we observed novel locus significantly associated with CHB (SNP: rs1264473, Gene: GRHL2, P = 1.57×10-6) and HCC (SNP: rs2833856, Gene: EVA1C, P = 1.62×10-6; SNP: rs4661093, Gene: ETV3, P = 2.26×10-6). In the trend study across progressive stages post HBV infection, one novel locus (SNP: rs1537862, Gene: LACE1, P = 1.85×10-6), and three MHC loci (HLA-DRB1, HLA-DPB1, HLA-DPA2) showed significant increased progressive risk from ASPI to CHB. Interestingly, underlying the evolutionary study of HBV-related genes in public database, we found that the derived allele of two HBV clearance related locus, rs3077 and rs9277542, are under strong selection in European population.

Conclusions: In this study, we identified several novel candidate genes associated with individual HBV infectious outcomes, progressive stages, and liver enzymes. Moreover, we identified two SNPs that show selective significance (HLA-DPA1, HLA-DPB1) in non-East Asian (European, American, South Asian) versus East Asian, indicating that host genetic factors contribute to the ethnic disparities of susceptibility of HBV infection. Taken together, these findings provided a new insight into the role of host genetic factors in HBV related outcomes and progression.

Comments

This study was supported by the National Natural Science Foundation of China (No. 61972007, No. 30671855), the International Science & Technology Cooperation Program of China (No. 2014DFR31200), Federal funds from the National Cancer Institute, National Institutes of Health, USA (No. N01-CO-12400), Shenzhen Municipal of Government of China (JCYJ20170412153248372, JCYJ20180507183615145).

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

ORCID ID

0000-0001-7353-8301

ResearcherID

N-1726-2015

DOI

10.21203/rs.3.rs-143403/v1

Peer Reviewed

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