title: Effects of HLA-DPB1 genotypes on chronic hepatitis B infection in Japanese individuals.
abstract: Significant associations of HLA-DP alleles with chronic hepatitis B (CHB) infection are evident in Asian and Arabian populations, including Japanese, Han Chinese, Korean, and Saudi Arabian populations. Here, significant associations between CHB infection and five DPB1 alleles (two susceptibility alleles, DPB1(*) 05:01 and (*) 09:01, and three protective alleles, DPB1(*) 02:01, (*) 04:01, and (*) 04:02) were confirmed in a population comprising of 2582 Japanese individuals. Furthermore, odds ratios for CHB were higher for those with both DPB1 susceptibility alleles than for those with only one susceptibility allele; therefore, effects of susceptibility alleles were additive for risk of CHB infection. Similarly, protective alleles showed an additive effect on protection from CHB infection. Moreover, heterozygotes of any protective allele showed stronger association with CHB than did homozygotes, suggesting that heterozygotes may bind a greater variety of hepatitis B-derived peptides, and thus present these peptides more efficiently to T-cell receptors than homozygotes. Notably, compound heterozygote of the protective allele (any one of DPB1*02:01, *04:01, and *04:02) and the susceptible allele DPB1*05:01 was significantly associated with protection against CHB infection, which indicates that one protective HLA-DPB1 molecule can provide dominant protection. Identification of the HLA-DPB1 genotypes associated with susceptibility to and protection from CHB infection is essential for future analysis of the mechanisms responsible for immune recognition of hepatitis B virus antigens by HLA-DPB1 molecules.
authors.affiliation: Department of Hepatic Disease, The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Chiba, Japan.|Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Nishida
authors.affiliation: Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Tokyo, Japan.
authors.forename: J
authors.initials: J
authors.lastname: Ohashi
authors.affiliation: Department of Hepatic Disease, The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Chiba, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Sugiyama
authors.affiliation: Department of Hepatic Disease, The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Chiba, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Tsuchiura
authors.affiliation: Department of Medical Chemistry, Kurume University School of Medicine, Kurume, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Yamamoto
authors.affiliation: Department of Hepatology and Pancreatology, Kawasaki Medical School, Kurashiki, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Hino
authors.affiliation: Department of Gastroenterology, Kanazawa University Graduate School of Medicine, Kanazawa, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Honda
authors.affiliation: Department of Gastroenterology, Kanazawa University Graduate School of Medicine, Kanazawa, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Kaneko
authors.affiliation: Clinical Research Center, National Nagasaki Medical Center, Nagasaki, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Yatsuhashi
authors.affiliation: Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Koike
authors.affiliation: Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: O
authors.initials: O
authors.lastname: Yokosuka
authors.affiliation: Department of Medicine, Shinshu University School of Medicine, Matsumoto, Japan.
authors.forename: E
authors.initials: E
authors.lastname: Tanaka
authors.affiliation: Department of Gastroenterological Surgery I, Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Taketomi
authors.affiliation: Division of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Kurosaki
authors.affiliation: Division of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Izumi
authors.affiliation: Department of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Sakamoto
authors.affiliation: Division of Hepatology, Saga Medical School, Saga, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Eguchi
authors.affiliation: Institute for Advanced Study, Kyushu University, Fukuoka, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Sasazuki
authors.affiliation: Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Tokunaga
authors.affiliation: Department of Hepatic Disease, The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Chiba, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Mizokami
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D044466:Asian People / Q000235:genetics; D002353:Carrier State / Q000453:epidemiology / Q000276:immunology; D002648:Child; D018450:Disease Progression; D005260:Female; D005787:Gene Frequency; D005802:Genes, MHC Class II; D020022:Genetic Predisposition to Disease; D005838:Genotype; D059868:HLA-DP beta-Chains / Q000235:genetics*; D019694:Hepatitis B, Chronic / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D055815:Young Adult
chemical_list: D059868:HLA-DP beta-Chains; C071170:HLA-DPB1 antigen
keywords: HLA-DPB1; chronic hepatitis B infection; hepatitis B virus; hepatocellular carcinoma