title: New susceptibility and resistance HLA-DP alleles to HBV-related diseases identified by a trans-ethnic association study in Asia.
abstract: Previous studies have revealed the association between SNPs located on human leukocyte antigen (HLA) class II genes, including HLA-DP and HLA-DQ, and chronic hepatitis B virus (HBV) infection, mainly in Asian populations. HLA-DP alleles or haplotypes associated with chronic HBV infection or disease progression have not been fully identified in Asian populations. We performed trans-ethnic association analyses of HLA-DPA1, HLA-DPB1 alleles and haplotypes with hepatitis B virus infection and disease progression among Asian populations comprising Japanese, Korean, Hong Kong, and Thai subjects. To assess the association between HLA-DP and chronic HBV infection and disease progression, we conducted high-resolution (4-digit) HLA-DPA1 and HLA-DPB1 genotyping in a total of 3,167 samples, including HBV patients, HBV-resolved individuals and healthy controls. Trans-ethnic association analyses among Asian populations identified a new risk allele HLA-DPB1*09 ∶ 01 (P = 1.36 × 10(-6); OR= 1.97; 95% CI, 1.50-2.59) and a new protective allele DPB1*02 ∶ 01 (P = 5.22 × 10(-6); OR = 0.68; 95% CI, 0.58-0.81) to chronic HBV infection, in addition to the previously reported alleles. Moreover, DPB1*02 ∶ 01 was also associated with a decreased risk of disease progression in chronic HBV patients among Asian populations (P = 1.55 × 10(-7); OR = 0.50; 95% CI, 0.39-0.65). Trans-ethnic association analyses identified Asian-specific associations of HLA-DP alleles and haplotypes with HBV infection or disease progression. The present findings will serve as a base for future functional studies of HLA-DP molecules in order to understand the pathogenesis of HBV infection and the development of hepatocellular carcinoma.
authors: The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Ichikawa, Chiba, Japan ; Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
authors: Nao
authors: N
authors: Nishida
authors: Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
authors: Hiromi
authors: H
authors: Sawai
authors: HLA Laboratory, Japanese Red Cross Kanto-Koshinetsu Block Blood Center, Koutou-ku, Tokyo, Japan.
authors: Koichi
authors: K
authors: Kashiwase
authors: HLA Laboratory, Japanese Red Cross Kanto-Koshinetsu Block Blood Center, Koutou-ku, Tokyo, Japan.
authors: Mutsuhiko
authors: M
authors: Minami
authors: The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Ichikawa, Chiba, Japan.
authors: Masaya
authors: M
authors: Sugiyama
authors: Department of Medicine, Queen Mary Hospital, Hong Kong.
authors: Wai-Kay
authors: WK
authors: Seto
authors: Department of Medicine, Queen Mary Hospital, Hong Kong.
authors: Man-Fung
authors: MF
authors: Yuen
authors: Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
authors: Nawarat
authors: N
authors: Posuwan
authors: Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
authors: Yong
authors: Y
authors: Poovorawan
authors: Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea.
authors: Sang Hoon
authors: SH
authors: Ahn
authors: Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea.
authors: Kwang-Hyub
authors: KH
authors: Han
authors: Department of Virology & Liver Unit, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, Japan.
authors: Kentaro
authors: K
authors: Matsuura
authors: Department of Virology & Liver Unit, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, Japan.
authors: Yasuhito
authors: Y
authors: Tanaka
authors: Division of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Musashino, Tokyo, Japan.
authors: Masayuki
authors: M
authors: Kurosaki
authors: Department of Liver Disease Control, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan ; Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan.
authors: Yasuhiro
authors: Y
authors: Asahina
authors: Division of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Musashino, Tokyo, Japan.
authors: Namiki
authors: N
authors: Izumi
authors: Department of Internal Medicine, Teine Keijinkai Hospital, Sapporo, Hokkaido, Japan.
authors: Jong-Hon
authors: JH
authors: Kang
authors: Department of Internal Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan.
authors: Shuhei
authors: S
authors: Hige
authors: Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Fukuoka, Japan.
authors: Tatsuya
authors: T
authors: Ide
authors: Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Okayama, Japan.
authors: Kazuhide
authors: K
authors: Yamamoto
authors: Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan.
authors: Isao
authors: I
authors: Sakaida
authors: Faculty of Medicine, Tottori University, Tottori, Tottori, Japan.
authors: Yoshikazu
authors: Y
authors: Murawaki
authors: Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Kyoto, Japan.
authors: Yoshito
authors: Y
authors: Itoh
authors: Department of Hepatology, Osaka City University Graduate School of Medicine, Osaka, Osaka, Japan.
authors: Akihiro
authors: A
authors: Tamori
authors: Department of Gastroenterology, Nagoya Daini Red Cross Hospital, Nagoya, Aichi, Japan.
authors: Etsuro
authors: E
authors: Orito
authors: Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Ehime, Japan.
authors: Yoichi
authors: Y
authors: Hiasa
authors: Department of Gastroenterology, Kanazawa University Graduate School of Medicine, Kanazawa, Ishikawa, Japan.
authors: Masao
authors: M
authors: Honda
authors: Department of Gastroenterology, Kanazawa University Graduate School of Medicine, Kanazawa, Ishikawa, Japan.
authors: Shuichi
authors: S
authors: Kaneko
authors: Department of Gastroenterology and Hepatology, National Hospital Organization Osaka National Hospital, Osaka, Osaka, Japan.
authors: Eiji
authors: E
authors: Mita
authors: Division of Gastroenterology and Hepatology, Department of Internal Medcine, Iwate Medical University, Morioka, Iwate, Japan.
authors: Kazuyuki
authors: K
authors: Suzuki
authors: Division of Hepatology and Pancreatology, Kawasaki Medical College, Kurashiki, Okayama, Japan.
authors: Keisuke
authors: K
authors: Hino
authors: Department of Medicine, Shinshu University School of Medicine, Matsumoto, Nagano, Japan.
authors: Eiji
authors: E
authors: Tanaka
authors: Division of Gastroenterology and Hepatology, Saitama Medical University, Iruma, Saitama, Japan.
authors: Satoshi
authors: S
authors: Mochida
authors: Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan.
authors: Masaaki
authors: M
authors: Watanabe
authors: Department of Internal Medicine, Saga Medical School, Saga, Saga, Japan.
authors: Yuichiro
authors: Y
authors: Eguchi
authors: The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Ichikawa, Chiba, Japan.
authors: Naohiko
authors: N
authors: Masaki
authors: The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Ichikawa, Chiba, Japan.
authors: Kazumoto
authors: K
authors: Murata
authors: The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Ichikawa, Chiba, Japan.
authors: Masaaki
authors: M
authors: Korenaga
authors: The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Ichikawa, Chiba, Japan.
authors: Yoriko
authors: Y
authors: Mawatari
authors: Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan.
authors: Jun
authors: J
authors: Ohashi
authors: Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
authors: Minae
authors: M
authors: Kawashima
authors: Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
authors: Katsushi
authors: K
authors: Tokunaga
authors: The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Ichikawa, Chiba, Japan.
authors: Masashi
authors: M
authors: Mizokami
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D001208:Asia; D060467:Disease Resistance / Q000235:genetics* / Q000276:immunology; D005006:Ethnicity / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006682:HLA-DP Antigens / Q000235:genetics; D006239:Haplotypes / Q000235:genetics; D006509:Hepatitis B / Q000235:genetics* / Q000276:immunology; D006515:Hepatitis B virus / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D055815:Young Adult
chemical_list: D006682:HLA-DP Antigens