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PLoS One. 2014 Feb 10;9(2):e86449. doi: 10.1371/journal.pone.0086449. eCollection 2014.

New susceptibility and resistance HLA-DP alleles to HBV-related diseases identified by a trans-ethnic association study in Asia.

Author information

1
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.
2
Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
3
HLA Laboratory, Japanese Red Cross Kanto-Koshinetsu Block Blood Center, Koutou-ku, Tokyo, Japan.
4
The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Ichikawa, Chiba, Japan.
5
Department of Medicine, Queen Mary Hospital, Hong Kong.
6
Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
7
Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea.
8
Department of Virology & Liver Unit, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, Japan.
9
Division of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Musashino, Tokyo, Japan.
10
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.
11
Department of Internal Medicine, Teine Keijinkai Hospital, Sapporo, Hokkaido, Japan.
12
Department of Internal Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Hokkaido, Japan.
13
Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Fukuoka, Japan.
14
Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama, Okayama, Japan.
15
Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan.
16
Faculty of Medicine, Tottori University, Tottori, Tottori, Japan.
17
Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto, Kyoto, Japan.
18
Department of Hepatology, Osaka City University Graduate School of Medicine, Osaka, Osaka, Japan.
19
Department of Gastroenterology, Nagoya Daini Red Cross Hospital, Nagoya, Aichi, Japan.
20
Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon, Ehime, Japan.
21
Department of Gastroenterology, Kanazawa University Graduate School of Medicine, Kanazawa, Ishikawa, Japan.
22
Department of Gastroenterology and Hepatology, National Hospital Organization Osaka National Hospital, Osaka, Osaka, Japan.
23
Division of Gastroenterology and Hepatology, Department of Internal Medcine, Iwate Medical University, Morioka, Iwate, Japan.
24
Division of Hepatology and Pancreatology, Kawasaki Medical College, Kurashiki, Okayama, Japan.
25
Department of Medicine, Shinshu University School of Medicine, Matsumoto, Nagano, Japan.
26
Division of Gastroenterology and Hepatology, Saitama Medical University, Iruma, Saitama, Japan.
27
Department of Gastroenterology, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan.
28
Department of Internal Medicine, Saga Medical School, Saga, Saga, Japan.
29
Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan.

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.

PMID:
24520320
PMCID:
PMC3919706
DOI:
10.1371/journal.pone.0086449
[Indexed for MEDLINE]
Free PMC Article

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