抄録
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.
| 元の言語 | English |
|---|---|
| ページ（範囲） | 864-871.e5 |
| ジャーナル | Gastroenterology |
| 巻 | 141 |
| 発行部数 | 3 |
| DOI | |
| 出版物ステータス | Published - 09-2011 |
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All Science Journal Classification (ASJC) codes
- Hepatology
- Gastroenterology
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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.
：: Gastroenterology, 巻 141, 番号 3, 09.2011, p. 864-871.e5.研究成果: Article
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 - 2011/9
Y1 - 2011/9
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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UR - http://www.scopus.com/inward/citedby.url?scp=80052111188&partnerID=8YFLogxK
U2 - 10.1053/j.gastro.2011.05.048
DO - 10.1053/j.gastro.2011.05.048
M3 - Article
C2 - 21699788
AN - SCOPUS:80052111188
VL - 141
SP - 864-871.e5
JO - Gastroenterology
JF - Gastroenterology
SN - 0016-5085
IS - 3
ER -