Large‐scale genome‐wide association study identifies HLA class II variants associated with chronic HBV infection: a study from Taiwan Biobank

• Published in: Alimentary pharmacology & therapeutics Vol. 52; no. 4; pp. 682 - 691
• Main Authors: Huang, Yu‐Han, Liao, Shu‐Fen, Khor, Seik‐Soon, Lin, Yu‐Ju, Chen, Hsuan‐Yu, Chang, Ya‐Hsuan, Huang, Yi‐Hsiang, Lu, Sheng‐Nan, Lee, Hye‐Won, Ko, Wen‐Ya, Huang, Claire, Liu, Po‐Chun, Chen, Yen‐Ju, Wu, Ping‐Feng, Chu, Hou‐Wei, Wu, Pei‐Ei, Tokunaga, Katsushi, Shen, Chen‐Yang, Lee, Mei‐Hsuan
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.08.2020
• Subjects: Adult; Aged; Alleles; Antigens; Biobanks; Biological Specimen Banks - statistics & numerical data; Chronic infection; DQA1 protein; Drb1 protein; Epitopes; Female; Gene Frequency; Genes, MHC Class II - genetics; Genetic diversity; Genetic Predisposition to Disease; Genome-wide association studies; Genome-Wide Association Study - methods; Genomes; Genotyping; Geographical variations; Hepatitis B; Hepatitis B Antibodies - blood; Hepatitis B surface antigen; Hepatitis B Surface Antigens - blood; Hepatitis B Surface Antigens - immunology; Hepatitis B, Chronic - blood; Hepatitis B, Chronic - epidemiology; Hepatitis B, Chronic - genetics; Histocompatibility antigen HLA; Humans; Infections; Male; Middle Aged; Nucleocapsids; Polymorphism, Single Nucleotide; Population genetics; Seroepidemiologic Studies; Serology; Single-nucleotide polymorphism; Taiwan - epidemiology; Taiwan
• ISSN: 0269-2813; 1365-2036; 1365-2036
• DOI: 10.1111/apt.15887

Summary Background Chronic hepatitis B virus (HBV) infection is a great health burden with geographical variations. Aims To explore genetic variants associated with chronic HBV infection. Methods The study included 15 352 participants seropositive for HBV core antibodies in Taiwan Biobank. Among them, 2591 (16.9%) seropositive for HBV surface antigen (HBsAg) were defined as having chronic HBV infection. All participants were examined for whole‐genome genotyping by Axiom‐Taiwan Biobank Array. The human leucocyte antigen (HLA) imputation was performed after identification of the variants within the region. Logistic regressions were used to estimate odds ratios (ORs) with 95% confidence intervals. Correlations of different HLA allele frequencies with HBsAg seroprevalence were evaluated across worldwide populations by Pearson correlation coefficients. Epitope prediction was performed for HLA alleles using NetMHCIIpan method. Results Located within a cluster of 450 single nucleotide polymorphisms in HLA class II, rs7770370 (P = 2.73 × 10−35) was significantly associated with HBV chronicity (Pcorrected < 8.6 × 10−8). Imputation analyses showed that HLA‐DPA1*02:02 and HLA‐DPB1*05:01 were associated with chronic HBV, with adjusted ORs of 1.43 (1.09‐1.89) and 1.61 (1.29‐2.01). These allele frequencies were positively correlated with global HBsAg seroprevalence, with R of 0.75 and 0.62 respectively (P < 0.05). HLA‐DRB1*13:02, HLA‐DQA1* 01:02 and HLA‐DQB1*06:09 associated with HBV chronicity negatively, with adjusted ORs of 0.31 (0.17‐0.58), 0.70 (0.56‐0.87) and 0.33 (0.18‐0.63). These HLA alleles had various binding affinities to the predicted epitopes derived from HBV nucleocapsid protein. Conclusions HLA class II variants are relevant for chronicity after HBV acquisition.