title: A genome-wide association study on chronic HBV infection and its clinical progression in male Han-Taiwanese.
abstract: It is common to observe the clustering of chronic hepatitis B surface antigen (HBsAg) carriers in families. Intra-familial transmission of hepatitis B virus (HBV) could be the reason for the familial clustering of HBsAg carriers. Additionally, genetic and gender factors have been reported to be involved. We conducted a three-stage genome-wide association study to identify genetic factors associated with chronic HBV susceptibility. A total of 1,065 male controls and 1,623 male HBsAg carriers were included. The whole-genome genotyping was done on Illumina HumanHap550 beadchips in 304 healthy controls and HumanHap610 beadchips in 321 cases. We found that rs9277535 (HLA-DPB1, P = 4.87×10(-14)), rs9276370 (HLA-DQA2, P = 1.9×10(-12)), rs7756516 and rs7453920 (HLA-DQB2, P = 1.48×10(-11) and P = 6.66×10(-15) respectively) were significantly associated with persistent HBV infection. A novel SNP rs9366816 near HLA-DPA3 also showed significant association (P = 2.58×10(-10)). The "T-T-G-G-T" haplotype of the five SNPs further signified their association with the disease (P = 1.48×10(-12); OR = 1.49). The "T-T" haplotype composed of rs7756516 and rs9276370 was more prevalent in severe disease subgroups and associated with non-sustained therapeutic response (P = 0.0262). The "G-C" haplotype was associated with sustained therapeutic response (P = 0.0132; OR = 2.49). We confirmed that HLA-DPB1, HLA-DQA2 and HLA-DQB2 loci were associated with persistent HBV infection in male Taiwan Han-Chinese. In addition, the HLA-DQA2 and -DQB2 complex was associated with clinical progression and therapeutic response.
authors.affiliation: Clinical Informatics and Medical Statistics Research Center, Chang Gung University College of Medicine, Taoyuan, Taiwan.
authors.forename: Su-Wei
authors.initials: SW
authors.lastname: Chang
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
authors.forename: Cathy Shen-Jang
authors.initials: CS
authors.lastname: Fann
authors.affiliation: Department of Biomedical Sciences, Graduate Institute of Biomedical Sciences, Chang Gung Molecular Medicine Research Center, Chang Gung University, Taoyuan, Taiwan.
authors.forename: Wen-Hui
authors.initials: WH
authors.lastname: Su
authors.affiliation: Division of Hepatology, Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou, Taiwan.
authors.forename: Yu Chen
authors.initials: YC
authors.lastname: Wang
authors.affiliation: Division of Hepatology, Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou, Taiwan.
authors.forename: Chia Chan
authors.initials: CC
authors.lastname: Weng
authors.affiliation: Department of Cell and Molecular Biology, College of Medicine and Molecular Medicine Research Center, Chang Gung University, Tao-Yuan, Taiwan.
authors.forename: Chia-Jung
authors.initials: CJ
authors.lastname: Yu
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
authors.forename: Chia-Lin
authors.initials: CL
authors.lastname: Hsu
authors.affiliation: Graduate Institute of Biostatistics, China Medical University, Taichung, Taiwan.
authors.forename: Ai-Ru
authors.initials: AR
authors.lastname: Hsieh
authors.affiliation: Division of Hepatology, Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou, Taiwan.
authors.forename: Rong-Nan
authors.initials: RN
authors.lastname: Chien
authors.affiliation: Division of Hepatology, Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou, Taiwan.
authors.forename: Chia-Ming
authors.initials: CM
authors.lastname: Chu
authors.affiliation: Division of Hepatology, Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou, Taiwan.
authors.forename: Dar-In
authors.initials: DI
authors.lastname: Tai
mesh_terms: D018450:Disease Progression; D005006:Ethnicity / Q000235:genetics*; D055106:Genome-Wide Association Study; D006239:Haplotypes / Q000235:genetics; D006514:Hepatitis B Surface Antigens / Q000276:immunology; D019694:Hepatitis B, Chronic / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology / Q000473:pathology*; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D015203:Reproducibility of Results; D013624:Taiwan; D016896:Treatment Outcome
chemical_list: D006514:Hepatitis B Surface Antigens