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Sci Rep. 2016 Apr 19;6:24767. doi: 10.1038/srep24767.

Understanding of HLA-conferred susceptibility to chronic hepatitis B infection requires HLA genotyping-based association analysis.

Author information

1
Department of Hepatic Disease, Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Chiba 272-8516, Japan.
2
Department of Human Genetics, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan.
3
Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Tokyo 113-0033, Japan.
4
Department of Hepatology and Pancreatology, Kawasaki Medical School, Okayama 701-0192, Japan.
5
Department of Gastroenterology, Kanazawa University Graduate School of Medicine, Ishikawa 920-0942, Japan.
6
Clinical Research Center, National Nagasaki Medical Center, Nagasaki 856-8562, Japan.
7
Department of Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University, Chiba 263-0022, Japan.
8
Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan.
9
Division of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo 180-0023, Japan.
10
Center for Gastroenterology, Teine Keijinkai Hospital, Hokkaido 006-0811, Japan.
11
Department of Medicine, Shinshu University School of Medicine, Nagano 390-0802, Japan.
12
Department of Gastroenterological Surgery I, Graduate School of Medicine, Hokkaido University, Hokkaido 060-0808, Japan.
13
Division of Hepatology, Saga Medical School, Saga 849-0937, Japan.
14
Department of Gastroenterology and Hepatology, Hokkaido University Graduate School of Medicine, Hokkaido 060-0808, Japan.
15
Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama 700-8558, Japan.
16
Department of Hepatology, Osaka City University Graduate School of Medicine, Osaka 558-8585, Japan.
17
Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Yamaguchi 753-8511, Japan.
18
Department of Hepatology, Sapporo-Kosei General Hospital, Hokkaido 060-0033, Japan.
19
Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kyoto 602-0841, Japan.
20
Division of Gastroenterology and Hepatology, Saitama Medical University, Saitama 350-0495, Japan.
21
Department of Gastroenterology and Hepatology, National Hospital Organization Osaka National Hospital, Osaka 540-0006, Japan.
22
Division of Hepatology, Department of Internal Medicine, Iwate Medical University, Iwate 020-8505, Japan.
23
Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Fukuoka 830-0011, Japan.
24
Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Ehime 791-0295, Japan.
25
HLA Foundation Laboratory, Kyoto 600-8813, Japan.
26
Department of Medical Biochemistry, Kurume University School of Medicine, Fukuoka 830-0011, Japan.
27
Institute for Advanced Study, Kyushu University, Fukuoka 819-0395, Japan.

Abstract

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.

PMID:
27091392
PMCID:
PMC4835786
DOI:
10.1038/srep24767
[Indexed for MEDLINE]
Free PMC Article

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