1. Amino acid position 37 of HLA-DRβ1 affects susceptibility to Crohn's disease in Asians.
- Author
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Han B, Akiyama M, Kim KK, Oh H, Choi H, Lee CH, Jung S, Lee HS, Kim EE, Cook S, Haritunians T, Yamazaki K, Park SH, Ye BD, McGovern DPB, Esaki M, Kawaguchi T, Khor SS, Taylor KD, Rotter JI, Suzuki Y, Matsui T, Motoya S, Bang SY, Kim TH, Momozawa Y, Kamatani Y, Tokunaga K, Kubo M, Okada Y, Yang SK, and Song K
- Subjects
- Alleles, Amino Acid Substitution genetics, Amino Acids chemistry, Amino Acids genetics, Asian People genetics, Colitis, Ulcerative pathology, Crohn Disease pathology, Female, Genetic Association Studies, Genotype, HLA-DRB1 Chains chemistry, Haplotypes genetics, Humans, Inflammatory Bowel Diseases pathology, Japan, Male, Protein Conformation, Republic of Korea, Colitis, Ulcerative genetics, Crohn Disease genetics, Genetic Predisposition to Disease, HLA-DRB1 Chains genetics, Inflammatory Bowel Diseases genetics
- 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]).
- Published
- 2018
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