The contribution of human leucocyte antigen complex genes to disease phenotype in ulcerative colitis

T. Ahmad; A. Armuzzi; M. Neville; M. Bunce; K. Ling; K. Welsh; S.E. Marshall; D.P. Jewell

doi:10.1046/j.1399-0039.2003.00129.x

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The contribution of human leucocyte antigen complex genes to disease phenotype in ulcerative colitis

Journal article

Peer reviewed

The contribution of human leucocyte antigen complex genes to disease phenotype in ulcerative colitis

T. Ahmad, A. Armuzzi, M. Neville, M. Bunce, K. Ling, K. Welsh, S.E. Marshall and D.P. Jewell

Tissue Antigens, Vol.62(6), pp.527-535

2003

DOI: https://doi.org/10.1046/j.1399-0039.2003.00129.x

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Abstract

Linkage and association studies implicate the human leucocyte antigen (HLA) region in genetic susceptibility to ulcerative colitis (UC). However, associations with specific variants have been inconsistent, even within defined ethnic groups. A genetic basis for the disease heterogeneity of UC may account for these discrepant findings from studies in unselected populations. Here, we examine the contribution of the HLA region to the clinical phenotype of UC. We studied 321 accurately phenotyped patients recruited from a single UK centre, with a median follow-up time of 15 years. Individuals were genotyped for 340 polymorphisms constructed into 25 gene-specific allelic haplotypes between HLA-A and Tapasin. Data were analysed with respect to age of onset, disease extent and severity. Strongest association with overall susceptibility was identified with HLA-DRB1 alleles replicating previous studies (DRB1*0103, DRB1*1502 and DRB1*0401). We report a novel association with homozygosity of a tumour necrosis factor (TNF) promoter haplotype (TNF-1031T, -863C, -857C, -380G, -308G and -238G) and distal disease extent that does not extend with time (distal vs total 40.9 vs 25.7%; RR = 2.0; 95% CI 1.23-3.24). We confirm the association of DRB1*0103 with total disease and/or disease requiring colectomy and further demonstrate that DRB1*0103 is associated with shorter time to surgery. Genes in the HLA play a role in modifying disease phenotype. Further studies are required to dissect how these genes functionally interact with each other and with environmental factors to determine clinical patterns of disease.

Details

Title: The contribution of human leucocyte antigen complex genes to disease phenotype in ulcerative colitis
Authors/Creators: T. Ahmad (Author/Creator) - University of Oxford
A. Armuzzi (Author/Creator) - University of Oxford
M. Neville (Author/Creator) - Cancer Research UK
M. Bunce (Author/Creator) - Biotech (Brazil)
K. Ling (Author/Creator) - University of Oxford
K. Welsh (Author/Creator) - Imperial College London
S.E. Marshall (Author/Creator) - Imperial College London
D.P. Jewell (Author/Creator) - University of Oxford
Publication Details: Tissue Antigens, Vol.62(6), pp.527-535
Publisher: Blackwell Publishing
Identifiers: 991005542566907891
Copyright: © 2003 Blackwell Munksgaard
Murdoch Affiliation: Murdoch University
Language: English
Resource Type: Journal article

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Collaboration types: Domestic collaboration
Citation topics: 1 Clinical & Life Sciences; 1.120 Inflammatory Bowel Diseases & Infections; 1.120.139 Inflammatory Bowel Disease
Web Of Science research areas: Cell Biology; Immunology; Pathology
ESI research areas: Molecular Biology & Genetics