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Hum Mol Genet. 2018 Nov 15;27(22):3901-3910. doi: 10.1093/hmg/ddy285.

Amino acid position 37 of HLA-DRβ1 affects susceptibility to Crohn's disease in Asians.

Author information

1
Department of Medicine, Seoul National University College of Medicine, Seoul, Korea.
2
Department of Convergence Medicine, University of Ulsan College of Medicine & Asan Institute for Life Sciences, Asan Medical Center, Seoul, Korea.
3
Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
4
Convergence Medicine Research Center and Biomedical Research Center, AILS, Asan Medical Center, Seoul, Korea.
5
Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul, Korea.
6
Department of Chemistry, Seoul National University, Seoul, Korea.
7
The F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
8
Division of Genomic Epidemiology and Clinical Trials, Clinical Trials Research Center, Nihon University School of Medicine, Tokyo, Japan.
9
Laboratory for Genotyping Development, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
10
Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
11
Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
12
Division of Gastroenterology, Department of Medicine, TokyoYamate Medical Center, Tokyo, Japan.
13
Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.
14
Human Genetics, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
15
Institute for Translational Genomics and Population Sciences,Los Angeles Biomedical Research Institute and Department of Pediatrics, Harbor-UCLA Medical CenterTorrance, CA, USA.
16
Department of Internal Medicine, Faculty of Medicine, Toho University, Chiba, Japan.
17
Department of Gastroenterology, Fukuoka University,Chikushi Hospital, Fukuoka, Japan.
18
Department of Gastroenterology, Sapporo-Kosei General Hospital, Sapporo, Japan.
19
Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, Korea.
20
Center for Genomic Medicine, Kyoto University Graduate School of Medicine,Sakyo-ku, Kyoto, Japan.
21
RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
22
Department of Statistical Genetics, Osaka University Graduate School of Medicine, Osaka, Japan.
23
Laboratory of Statistical Immunology, Immunology Frontier Research Center (WPI-IFReC), Osaka University, Osaka, Japan.

Abstract

Crohn's disease (CD) and ulcerative colitis (UC) are the major types of chronic inflammatory bowel disease (IBD) characterized by recurring episodes of inflammation of the gastrointestinal tract. Although it is well established that human leukocyte antigen (HLA) is a major risk factor for IBD, it is yet to be determined which HLA alleles or amino acids drive the risks of CD and UC in Asians. To define the roles of HLA for IBD in Asians, we fine-mapped HLA in 12 568 individuals from Korea and Japan (3294 patients with CD, 1522 patients with UC and 7752 controls). We identified that the amino acid position 37 of HLA-DRβ1 plays a key role in the susceptibility to CD (presence of serine being protective, P = 3.6 × 10-67, OR = 0.48 [0.45-0.52]). For UC, we confirmed the known association of the haplotype spanning HLA-C*12:02, HLA-B*52:01 and HLA-DRB1*1502 (P = 1.2 × 10-28, OR = 4.01 [3.14-5.12]).

PMID:
30084967
DOI:
10.1093/hmg/ddy285
[Indexed for MEDLINE]

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