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

Buhm Han; Masato Akiyama; Kyung Kon Kim; Hyunjung Oh; Hyunchul Choi; Cue Hyunkyu Lee; Seulgi Jung; Ho Su Lee; Emma E. Kim; Seungho Cook; Talin Haritunians; Keiko Yamazaki; Sang Hyoung Park; Byong Duk Ye; Dermot P.B. McGovern; Motohiro Esaki; Takaaki Kawaguchi; Seik Soon Khor; Kent D. Taylor; Jerome I. Rotter; Yasuo Suzuki; Toshiyuki Matsui; Satoshi Motoya; So Young Bang; Tae Hwan Kim; Yukihide Momozawa; Yoichiro Kamatani; Katsushi Tokunaga; Michiaki Kubo; Yukinori Okada; Suk Kyun Yang; Kyuyoung Song

doi:10.1093/hmg/ddy285

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

Buhm Han, Masato Akiyama, Kyung Kon Kim, Hyunjung Oh, Hyunchul Choi, Cue Hyunkyu Lee, Seulgi Jung, Ho Su Lee, Emma E. Kim, Seungho Cook, Talin Haritunians, Keiko Yamazaki, Sang Hyoung Park, Byong Duk Ye, Dermot P.B. McGovern, Motohiro Esaki, Takaaki Kawaguchi, Seik Soon Khor, Kent D. Taylor, Jerome I. RotterYasuo Suzuki, Toshiyuki Matsui, Satoshi Motoya, So Young Bang, Tae Hwan Kim, Yukihide Momozawa, Yoichiro Kamatani, Katsushi Tokunaga, Michiaki Kubo, Yukinori Okada, Suk Kyun Yang, Kyuyoung Song

Research output: Contribution to journal › Article › peer-review

16 Scopus citations

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]).

Original language	English
Pages (from-to)	3901-3910
Number of pages	10
Journal	Human Molecular Genetics
Volume	27
Issue number	22
DOIs	https://doi.org/10.1093/hmg/ddy285
State	Published - 1 Nov 2018
Externally published	Yes

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Han, B., Akiyama, M., Kim, K. K., Oh, H., Choi, H., Lee, C. H., Jung, S., Lee, H. S., Kim, E. E., Cook, S., Haritunians, T., Yamazaki, K., Park, S. H., Ye, B. D., McGovern, D. P. B., Esaki, M., Kawaguchi, T., Khor, S. S., Taylor, K. D., ... Song, K. (2018). Amino acid position 37 of HLA-DRβ1 affects susceptibility to Crohn's disease in Asians. Human Molecular Genetics, 27(22), 3901-3910. https://doi.org/10.1093/hmg/ddy285

@article{6b506dce42f9419da5fc3b674ff73af2,

title = "Amino acid position 37 of HLA-DRβ1 affects susceptibility to Crohn's disease in Asians",

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]).",

author = "Buhm Han and Masato Akiyama and Kim, {Kyung Kon} and Hyunjung Oh and Hyunchul Choi and Lee, {Cue Hyunkyu} and Seulgi Jung and Lee, {Ho Su} and Kim, {Emma E.} and Seungho Cook and Talin Haritunians and Keiko Yamazaki and Park, {Sang Hyoung} and Ye, {Byong Duk} and McGovern, {Dermot P.B.} and Motohiro Esaki and Takaaki Kawaguchi and Khor, {Seik Soon} and Taylor, {Kent D.} and Rotter, {Jerome I.} and Yasuo Suzuki and Toshiyuki Matsui and Satoshi Motoya and Bang, {So Young} and Kim, {Tae Hwan} and Yukihide Momozawa and Yoichiro Kamatani and Katsushi Tokunaga and Michiaki Kubo and Yukinori Okada and Yang, {Suk Kyun} and Kyuyoung Song",

year = "2018",

month = nov,

day = "1",

doi = "10.1093/hmg/ddy285",

language = "English",

volume = "27",

pages = "3901--3910",

journal = "Human Molecular Genetics",

issn = "0964-6906",

publisher = "Oxford University Press",

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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 & Song, K 2018, 'Amino acid position 37 of HLA-DRβ1 affects susceptibility to Crohn's disease in Asians', Human Molecular Genetics, vol. 27, no. 22, pp. 3901-3910. https://doi.org/10.1093/hmg/ddy285

TY - JOUR

T1 - Amino acid position 37 of HLA-DRβ1 affects susceptibility to Crohn's disease in Asians

AU - Han, Buhm

AU - Akiyama, Masato

AU - Kim, Kyung Kon

AU - Oh, Hyunjung

AU - Choi, Hyunchul

AU - Lee, Cue Hyunkyu

AU - Jung, Seulgi

AU - Lee, Ho Su

AU - Kim, Emma E.

AU - Cook, Seungho

AU - Haritunians, Talin

AU - Yamazaki, Keiko

AU - Park, Sang Hyoung

AU - Ye, Byong Duk

AU - McGovern, Dermot P.B.

AU - Esaki, Motohiro

AU - Kawaguchi, Takaaki

AU - Khor, Seik Soon

AU - Taylor, Kent D.

AU - Rotter, Jerome I.

AU - Suzuki, Yasuo

AU - Matsui, Toshiyuki

AU - Motoya, Satoshi

AU - Bang, So Young

AU - Kim, Tae Hwan

AU - Momozawa, Yukihide

AU - Kamatani, Yoichiro

AU - Tokunaga, Katsushi

AU - Kubo, Michiaki

AU - Okada, Yukinori

AU - Yang, Suk Kyun

AU - Song, Kyuyoung

PY - 2018/11/1

Y1 - 2018/11/1

N2 - 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]).

AB - 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]).

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U2 - 10.1093/hmg/ddy285

DO - 10.1093/hmg/ddy285

M3 - Article

C2 - 30084967

AN - SCOPUS:85056257724

SN - 0964-6906

VL - 27

SP - 3901

EP - 3910

JO - Human Molecular Genetics

JF - Human Molecular Genetics

IS - 22

ER -

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

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