HLA-Cw (*)1202-B (*)5201-DRB1 (*)1502 haplotype increases risk for ulcerative colitis but reduces risk for crohn's disease

Yukinori Okada, Keiko Yamazaki, Junji Umeno, Atsushi Takahashi, Natsuhiko Kumasaka, Kyota Ashikawa, Tomomi Aoi, Masakazu Takazoe, Toshiyuki Matsui, Atsushi Hirano, Takayuki Matsumoto, Naoyuki Kamatani, Yusuke Nakamura, Kazuhiko Yamamoto, Michiaki Kubo

Research output: Contribution to journalArticle

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Abstract

Background & Aims: There are many genetic factors that are associated with both ulcerative colitis (UC) and Crohn's disease (CD). However, genetic factors that have distinct effects on UC and CD have not been examined. Methods: We performed a comparative genome-wide association study (GWAS) and a replication study using data from 748 patients with UC and 979 with CD, selected from a Japanese population. We conducted high-resolution (4-digit) genotyping of human leukocyte antigen (HLA) alleles in patients with UC and CD and additional 905 healthy individuals (controls). We performed haplotype-based analysis using data from the GWAS and HLA alleles to associate them with UC or CD. Results: The comparative GWAS and the replication study identified significant associations in the major histocompatibility complex region at 6p21 with UC and CD (rs9271366, P = 1.6 × 1070; odds ratio [OR] = 4.44). Haplotype-based analysis in the major histocompatibility complex region showed that HLA-Cw (*)1202-B (*)5201-DRB1 (*)1502 haplotype was significantly associated with increased risk of UC compared with CD (P = 1.1 × 10-33; OR = 6.58), accounting for most of the associations observed in the GWAS. Compared with the controls, this HLA haplotype significantly increases susceptibility to UC (P = 4.0 × 10-21; OR = 2.65), but reduces risk for CD (P = 1.1 × 10-7; OR = 0.40). Distinct effects of this HLA haplotype on UC and CD were independent of other HLA alleles and haplotypes (P = 2.0 × 10-19 and P = 7.2 × 10-5, respectively). Conclusions: The HLA-Cw (*)1202-B (*)5201-DRB1 (*)1502 haplotype increases susceptibility to UC but reduces risk for CD, based on a GWAS of a Japanese population.

Original languageEnglish
JournalGastroenterology
Volume141
Issue number3
DOIs
Publication statusPublished - 01-01-2011
Externally publishedYes

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HLA Antigens
Ulcerative Colitis
Crohn Disease
Haplotypes
Genome-Wide Association Study
Odds Ratio
Alleles
Major Histocompatibility Complex
Population

All Science Journal Classification (ASJC) codes

  • Hepatology
  • Gastroenterology

Cite this

Okada, Yukinori ; Yamazaki, Keiko ; Umeno, Junji ; Takahashi, Atsushi ; Kumasaka, Natsuhiko ; Ashikawa, Kyota ; Aoi, Tomomi ; Takazoe, Masakazu ; Matsui, Toshiyuki ; Hirano, Atsushi ; Matsumoto, Takayuki ; Kamatani, Naoyuki ; Nakamura, Yusuke ; Yamamoto, Kazuhiko ; Kubo, Michiaki. / HLA-Cw (*)1202-B (*)5201-DRB1 (*)1502 haplotype increases risk for ulcerative colitis but reduces risk for crohn's disease. In: Gastroenterology. 2011 ; Vol. 141, No. 3.
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abstract = "Background & Aims: There are many genetic factors that are associated with both ulcerative colitis (UC) and Crohn's disease (CD). However, genetic factors that have distinct effects on UC and CD have not been examined. Methods: We performed a comparative genome-wide association study (GWAS) and a replication study using data from 748 patients with UC and 979 with CD, selected from a Japanese population. We conducted high-resolution (4-digit) genotyping of human leukocyte antigen (HLA) alleles in patients with UC and CD and additional 905 healthy individuals (controls). We performed haplotype-based analysis using data from the GWAS and HLA alleles to associate them with UC or CD. Results: The comparative GWAS and the replication study identified significant associations in the major histocompatibility complex region at 6p21 with UC and CD (rs9271366, P = 1.6 × 1070; odds ratio [OR] = 4.44). Haplotype-based analysis in the major histocompatibility complex region showed that HLA-Cw (*)1202-B (*)5201-DRB1 (*)1502 haplotype was significantly associated with increased risk of UC compared with CD (P = 1.1 × 10-33; OR = 6.58), accounting for most of the associations observed in the GWAS. Compared with the controls, this HLA haplotype significantly increases susceptibility to UC (P = 4.0 × 10-21; OR = 2.65), but reduces risk for CD (P = 1.1 × 10-7; OR = 0.40). Distinct effects of this HLA haplotype on UC and CD were independent of other HLA alleles and haplotypes (P = 2.0 × 10-19 and P = 7.2 × 10-5, respectively). Conclusions: The HLA-Cw (*)1202-B (*)5201-DRB1 (*)1502 haplotype increases susceptibility to UC but reduces risk for CD, based on a GWAS of a Japanese population.",
author = "Yukinori Okada and Keiko Yamazaki and Junji Umeno and Atsushi Takahashi and Natsuhiko Kumasaka and Kyota Ashikawa and Tomomi Aoi and Masakazu Takazoe and Toshiyuki Matsui and Atsushi Hirano and Takayuki Matsumoto and Naoyuki Kamatani and Yusuke Nakamura and Kazuhiko Yamamoto and Michiaki Kubo",
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Okada, Y, Yamazaki, K, Umeno, J, Takahashi, A, Kumasaka, N, Ashikawa, K, Aoi, T, Takazoe, M, Matsui, T, Hirano, A, Matsumoto, T, Kamatani, N, Nakamura, Y, Yamamoto, K & Kubo, M 2011, 'HLA-Cw (*)1202-B (*)5201-DRB1 (*)1502 haplotype increases risk for ulcerative colitis but reduces risk for crohn's disease', Gastroenterology, vol. 141, no. 3. https://doi.org/10.1053/j.gastro.2011.05.048

HLA-Cw (*)1202-B (*)5201-DRB1 (*)1502 haplotype increases risk for ulcerative colitis but reduces risk for crohn's disease. / Okada, Yukinori; Yamazaki, Keiko; Umeno, Junji; Takahashi, Atsushi; Kumasaka, Natsuhiko; Ashikawa, Kyota; Aoi, Tomomi; Takazoe, Masakazu; Matsui, Toshiyuki; Hirano, Atsushi; Matsumoto, Takayuki; Kamatani, Naoyuki; Nakamura, Yusuke; Yamamoto, Kazuhiko; Kubo, Michiaki.

In: Gastroenterology, Vol. 141, No. 3, 01.01.2011.

Research output: Contribution to journalArticle

TY - JOUR

T1 - HLA-Cw (*)1202-B (*)5201-DRB1 (*)1502 haplotype increases risk for ulcerative colitis but reduces risk for crohn's disease

AU - Okada, Yukinori

AU - Yamazaki, Keiko

AU - Umeno, Junji

AU - Takahashi, Atsushi

AU - Kumasaka, Natsuhiko

AU - Ashikawa, Kyota

AU - Aoi, Tomomi

AU - Takazoe, Masakazu

AU - Matsui, Toshiyuki

AU - Hirano, Atsushi

AU - Matsumoto, Takayuki

AU - Kamatani, Naoyuki

AU - Nakamura, Yusuke

AU - Yamamoto, Kazuhiko

AU - Kubo, Michiaki

PY - 2011/1/1

Y1 - 2011/1/1

N2 - Background & Aims: There are many genetic factors that are associated with both ulcerative colitis (UC) and Crohn's disease (CD). However, genetic factors that have distinct effects on UC and CD have not been examined. Methods: We performed a comparative genome-wide association study (GWAS) and a replication study using data from 748 patients with UC and 979 with CD, selected from a Japanese population. We conducted high-resolution (4-digit) genotyping of human leukocyte antigen (HLA) alleles in patients with UC and CD and additional 905 healthy individuals (controls). We performed haplotype-based analysis using data from the GWAS and HLA alleles to associate them with UC or CD. Results: The comparative GWAS and the replication study identified significant associations in the major histocompatibility complex region at 6p21 with UC and CD (rs9271366, P = 1.6 × 1070; odds ratio [OR] = 4.44). Haplotype-based analysis in the major histocompatibility complex region showed that HLA-Cw (*)1202-B (*)5201-DRB1 (*)1502 haplotype was significantly associated with increased risk of UC compared with CD (P = 1.1 × 10-33; OR = 6.58), accounting for most of the associations observed in the GWAS. Compared with the controls, this HLA haplotype significantly increases susceptibility to UC (P = 4.0 × 10-21; OR = 2.65), but reduces risk for CD (P = 1.1 × 10-7; OR = 0.40). Distinct effects of this HLA haplotype on UC and CD were independent of other HLA alleles and haplotypes (P = 2.0 × 10-19 and P = 7.2 × 10-5, respectively). Conclusions: The HLA-Cw (*)1202-B (*)5201-DRB1 (*)1502 haplotype increases susceptibility to UC but reduces risk for CD, based on a GWAS of a Japanese population.

AB - Background & Aims: There are many genetic factors that are associated with both ulcerative colitis (UC) and Crohn's disease (CD). However, genetic factors that have distinct effects on UC and CD have not been examined. Methods: We performed a comparative genome-wide association study (GWAS) and a replication study using data from 748 patients with UC and 979 with CD, selected from a Japanese population. We conducted high-resolution (4-digit) genotyping of human leukocyte antigen (HLA) alleles in patients with UC and CD and additional 905 healthy individuals (controls). We performed haplotype-based analysis using data from the GWAS and HLA alleles to associate them with UC or CD. Results: The comparative GWAS and the replication study identified significant associations in the major histocompatibility complex region at 6p21 with UC and CD (rs9271366, P = 1.6 × 1070; odds ratio [OR] = 4.44). Haplotype-based analysis in the major histocompatibility complex region showed that HLA-Cw (*)1202-B (*)5201-DRB1 (*)1502 haplotype was significantly associated with increased risk of UC compared with CD (P = 1.1 × 10-33; OR = 6.58), accounting for most of the associations observed in the GWAS. Compared with the controls, this HLA haplotype significantly increases susceptibility to UC (P = 4.0 × 10-21; OR = 2.65), but reduces risk for CD (P = 1.1 × 10-7; OR = 0.40). Distinct effects of this HLA haplotype on UC and CD were independent of other HLA alleles and haplotypes (P = 2.0 × 10-19 and P = 7.2 × 10-5, respectively). Conclusions: The HLA-Cw (*)1202-B (*)5201-DRB1 (*)1502 haplotype increases susceptibility to UC but reduces risk for CD, based on a GWAS of a Japanese population.

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DO - 10.1053/j.gastro.2011.05.048

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