title: Protective effects of HLA-DPA1/DPB1 variants against Hepatitis B virus infection in an Indonesian population.
abstract: Human leukocyte antigen (HLA) DPA1/DPB1 variants have been reported to influence Hepatitis B virus (HBV) infection. HLA-DPA1/DPB1 plays a pivotal role in antigen presentation to CD4(+) helper T cells and influences the outcome of HBV infection. To investigate the influence of HLA-DP variants on the outcome of HBV infection in an Indonesian population where it has the third-highest prevalence of HBV infection worldwide, we performed a case-control study of 686 participants, including patients with HBV-related advanced or nonadvanced liver disease, patients with spontaneously resolved HBV, and healthy controls. Single-nucleotide polymorphisms in HLA-DPA1 (rs3077) and HLA-DPB1 (rs3135021, rs9277535, and rs228388) were genotyped using real-time TaqMan® genotyping assays. Because rs2281388 deviated from Hardy-Weinberg equilibrium, it was excluded from subsequent analyses. The results of logistic regression analyses showed that the HLA-DPB1 rs9277535 variants were associated with a reduced risk of persistent HBV infection (odds ratio [OR] 0.70, 95% confidence interval [95% CI] 0.52-0.96, P=0.026, additive genetic model; OR 0.60, 95% CI 0.38-0.96, P=0.033, dominant genetic model). The HLA-DPA1 rs3077 variant was associated with a protective effect increasing the spontaneously resolved HBV infection (OR 0.64, 95% CI 0.41-0.98, P=0.039, dominant genetic model). By contrast, the HLA-DPB1 rs3135021 variant was not associated with the outcome of HBV infection, including susceptibility, spontaneously resolved, or disease progression. Combinations of haplotype markers were also associated with HBV susceptibility (CA for rs3077-rs9277535, OR 0.57, 95% CI 0.36-0.92, P=0.021; GA for rs3135021-rs9277535, OR 0.56, 95% CI 0.36-0.86, P=0.0087). In conclusion, these findings confirm that HLA-DPA1/DPB1 variants were associated with the outcomes of HBV infection in an Indonesian population.
authors.affiliation: Division of Molecular Medicine & Medical Genetics, Department of Pathology, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan; Division of Infectious Disease Pathology, Department of Microbiology and Infectious Diseases, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan; Department of Physiology, Faculty of Medicine, Gadjah Mada University, Yogyakarta 55281, Indonesia.
authors.forename: Widya
authors.initials: W
authors.lastname: Wasityastuti
authors.affiliation: Department of Gastroenterology, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan. Electronic address: yanoyo@med.kobe-u.ac.jp.
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Yano
authors.affiliation: Subdivision of Gastroenterohepatology, Department of Internal Medicine, Dr. Sardjito Hospital, Faculty of Medicine, Gadjah Mada University, Yogyakarta 55281, Indonesia.
authors.forename: Neneng
authors.initials: N
authors.lastname: Ratnasari
authors.affiliation: Department of Clinical Pathology, Dr. Sardjito Hospital, Faculty of Medicine, Gadjah Mada University, Yogyakarta 55281, Indonesia.
authors.forename: Teguh
authors.initials: T
authors.lastname: Triyono
authors.affiliation: Subdivision of Gastroenterohepatology, Department of Internal Medicine, Dr. Sardjito Hospital, Faculty of Medicine, Gadjah Mada University, Yogyakarta 55281, Indonesia.
authors.forename: Catharina
authors.initials: C
authors.lastname: Triwikatmani
authors.affiliation: Subdivision of Gastroenterohepatology, Department of Internal Medicine, Dr. Sardjito Hospital, Faculty of Medicine, Gadjah Mada University, Yogyakarta 55281, Indonesia.
authors.forename: Fahmi
authors.initials: F
authors.lastname: Indrarti
authors.affiliation: Department of Anatomical Pathology, Dr. Sardjito Hospital, Faculty of Medicine, Gadjah Mada University, Yogyakarta 55281, Indonesia.
authors.forename: Didik Setyo
authors.initials: DS
authors.lastname: Heriyanto
authors.affiliation: Division of Molecular Medicine & Medical Genetics, Department of Pathology, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan; Division of Infectious Disease Pathology, Department of Microbiology and Infectious Diseases, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.
authors.forename: Laura Navika
authors.initials: LN
authors.lastname: Yamani
authors.affiliation: Division of Molecular Medicine & Medical Genetics, Department of Pathology, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan; Division of Infectious Disease Pathology, Department of Microbiology and Infectious Diseases, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.
authors.forename: Yujiao
authors.initials: Y
authors.lastname: Liang
authors.affiliation: Center for Infectious Diseases, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan; Indonesia-Japan Collaborative Research Centre for Emerging and Re-emerging Infectious Disease, Institute of Tropical Disease, Airlangga University, Surabaya 60115, Indonesia.
authors.forename: Takako
authors.initials: T
authors.lastname: Utsumi
authors.affiliation: Division of Molecular Medicine & Medical Genetics, Department of Pathology, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan; Division of Infectious Disease Pathology, Department of Microbiology and Infectious Diseases, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.
authors.forename: Yoshitake
authors.initials: Y
authors.lastname: Hayashi
mesh_terms: D000328:Adult; D000483:Alleles; D016022:Case-Control Studies; D005260:Female; D015870:Gene Expression; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D059867:HLA-DP alpha-Chains / Q000235:genetics* / Q000276:immunology; D059868:HLA-DP beta-Chains / Q000235:genetics* / Q000276:immunology; D006239:Haplotypes; D006515:Hepatitis B virus / Q000235:genetics* / Q000254:growth & development / Q000302:isolation & purification; D019694:Hepatitis B, Chronic / Q000235:genetics* / Q000276:immunology / Q000821:virology; D006801:Humans; D007214:Indonesia; D008297:Male; D008875:Middle Aged; D008957:Models, Genetic; D020641:Polymorphism, Single Nucleotide; D065840:Protective Factors; D012075:Remission, Spontaneous; D012720:Severity of Illness Index
chemical_list: D059867:HLA-DP alpha-Chains; D059868:HLA-DP beta-Chains; C071172:HLA-DPA1 antigen; C071170:HLA-DPB1 antigen
keywords: HBV infection; HLA-DP variants; Host gene; Indonesian population; Protection