Understanding of HLA-conferred susceptibility to chronic hepatitis B infection requires HLA genotyping-based association analysis.
Associations of variants located in the HLA class II region with chronic hepatitis B (CHB) infection have been identified in Asian populations. Here, HLA imputation method was applied to determine HLA alleles using genome-wide SNP typing data of 1,975 Japanese individuals (1,033 HBV patients and 942 healthy controls). Together with data of an additional 1,481 Japanese healthy controls, association tests of six HLA loci including HLA-A, C, B, DRB1, DQB1, and DPB1, were performed. Although the strongest association was detected at a SNP located in the HLA-DP locus in a SNP-based GWAS using data from the 1,975 Japanese individuals, HLA genotyping-based analysis identified DQB1*06:01 as having the strongest association, showing a greater association with CHB susceptibility (OR = 1.76, P = 6.57 × 10(-18)) than any one of five HLA-DPB1 alleles that were previously reported as CHB susceptibility alleles. Moreover, HLA haplotype analysis showed that, among the five previously reported HLA-DPB1 susceptibility and protective alleles, the association of two DPB1 alleles (DPB1*09:01, and *04:01) had come from linkage disequilibrium with HLA-DR-DQ haplotypes, DRB1*15:02-DQB1*06:01 and DRB1*13:02-DQB1*06:04, respectively. The present study showed an example that SNP-based GWAS does not necessarily detect the primary susceptibility locus in the HLA region.
Department of Hepatic Disease, Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Chiba 272-8516, Japan.|Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan.
Nao
N
Nishida
Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Tokyo 113-0033, Japan.
Jun
J
Ohashi
Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan.
Seik-Soon
SS
Khor
Department of Hepatic Disease, Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Chiba 272-8516, Japan.
Masaya
M
Sugiyama
Department of Hepatic Disease, Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Chiba 272-8516, Japan.
Takayo
T
Tsuchiura
Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan.
Hiromi
H
Sawai
Department of Hepatology and Pancreatology, Kawasaki Medical School, Okayama 701-0192, Japan.
Keisuke
K
Hino
Department of Gastroenterology, Kanazawa University Graduate School of Medicine, Ishikawa 920-0942, Japan.
Masao
M
Honda
Department of Gastroenterology, Kanazawa University Graduate School of Medicine, Ishikawa 920-0942, Japan.
Shuichi
S
Kaneko
Clinical Research Center, National Nagasaki Medical Center, Nagasaki 856-8562, Japan.
Hiroshi
H
Yatsuhashi
Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba 263-0022, Japan.
Osamu
O
Yokosuka
Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan.
Kazuhiko
K
Koike
Division of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo 180-0023, Japan.
Masayuki
M
Kurosaki
Division of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo 180-0023, Japan.
Namiki
N
Izumi
Department of Hepatic Disease, Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Chiba 272-8516, Japan.
Masaaki
M
Korenaga
Center for Gastroenterology, Teine Keijinkai Hospital, Hokkaido 006-0811, Japan.
Jong-Hon
JH
Kang
Department of Medicine, Shinshu University School of Medicine, Nagano 390-0802, Japan.
Eiji
E
Tanaka
Department of Gastroenterological Surgery I, Graduate School of Medicine, Hokkaido University, Hokkaido 060-0808, Japan.
Akinobu
A
Taketomi
Division of Hepatology, Saga Medical School, Saga 849-0937, Japan.
Yuichiro
Y
Eguchi
Department of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, Hokkaido 060-0808, Japan.
Naoya
N
Sakamoto
Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama 700-8558, Japan.
Kazuhide
K
Yamamoto
Department of Hepatology, Osaka City University Graduate School of Medicine, Osaka 558-8585, Japan.
Akihiro
A
Tamori
Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Yamaguchi 753-8511, Japan.
Isao
I
Sakaida
Department of Hepatology, Sapporo-Kosei General Hospital, Hokkaido 060-0033, Japan.
Shuhei
S
Hige
Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto 602-0841, Japan.
Yoshito
Y
Itoh
Division of Gastroenterology and Hepatology, Saitama Medical University, Saitama 350-0495, Japan.
Satoshi
S
Mochida
Department of Gastroenterology and Hepatology, National Hospital Organization Osaka National Hospital, Osaka 540-0006, Japan.
Eiji
E
Mita
Division of Hepatology, Department of Internal Medicine, Iwate Medical University, Iwate 020-8505, Japan.
Yasuhiro
Y
Takikawa
Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Fukuoka 830-0011, Japan.
Tatsuya
T
Ide
Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Ehime 791-0295, Japan.
Yoichi
Y
Hiasa
HLA Foundation Laboratory, Kyoto 600-8813, Japan.
Hiroto
H
Kojima
Department of Medical Biochemistry, Kurume University School of Medicine, Fukuoka 830-0011, Japan.
Ken
K
Yamamoto
Clinical Research Center, National Nagasaki Medical Center, Nagasaki 856-8562, Japan.
Minoru
M
Nakamura
HLA Foundation Laboratory, Kyoto 600-8813, Japan.
Hiroh
H
Saji
Institute for Advanced Study, Kyushu University, Fukuoka 819-0395, Japan.
Takehiko
T
Sasazuki
Department of Hepatic Disease, Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Chiba 272-8516, Japan.
Tatsuya
T
Kanto
Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan.
Katsushi
K
Tokunaga
Department of Hepatic Disease, Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Chiba 272-8516, Japan.
Masashi
M
Mizokami
D004198:Disease Susceptibility; D005838:Genotype; D006680:HLA Antigens / Q000235:genetics / Q000276:immunology*; D006239:Haplotypes; D019694:Hepatitis B, Chronic / Q000235:genetics / Q000276:immunology*; D006801:Humans; D015810:Linkage Disequilibrium; D020641:Polymorphism, Single Nucleotide
D006680:HLA Antigens