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Gastroenterology. 2011 Sep;141(3):864-871.e1-5. doi: 10.1053/j.gastro.2011.05.048. Epub 2011 Jul 19.

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

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  • 1Laboratory for Statistical Analysis, Center for Genomic Medicine, RIKEN, Yokohama Institute, Japan.

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 × 10⁻⁷⁰; 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.

Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.

PMID:
21699788
[PubMed - indexed for MEDLINE]
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