Evidence for genetic heterogeneity in inflammatory bowel disease (IBD); HLA genes in the predisposition to suffer from ulcerative colitis (UC) and Crohn's disease (CD)

Author:

BOUMA G1,OUDKERK POOL M2,CRUSIUS J B A1,TH SCHREUDER G M3,HELLEMANS H P R1,MEIJER B U G A1,KOSTENSE P J4,GIPHART M J3,MEUWISSEN S G M1,PEÑA A S1

Affiliation:

1. Department of Gastroenterology

2. Department of Internal Medicine, Ziekenhuis De Weezenlanden, Zwolle

3. Department of Immunohaematology and Bloodbank, Academic Hospital Leiden, Leiden, The Netherlands

4. Department of Epidemiology and Biostatistics, Academic Hospital Vrije Universiteit Amsterdam

Abstract

SUMMARY Family and epidemiological studies support a genetic susceptibility to UC and CD. Conflicting reports regarding associations between UC and HLA-DR2 and between CD and various HLA alleles have been published. The aim of this study was to determine whether molecularly defined HLA-DR genes are associated with these diseases in a Dutch group of patients. Fifty-nine unrelated Dutch UC patients and 89 CD patients were typed using DNA-based methods. A total of 2400 healthy local blood donors served as controls. The phenotype frequency of the HLA-DRB1*15 allele was increased in UC patients compared with controls (42% versus 26% in controls; P = 0.006; odds ratio (OR) = 2.1), and was predominantly found in female patients (53% versus 24%; P = 0.001; OR = 3.5). The DRB1*15 allele was increased in UC patients having a positive family history (P = 0.01; OR = 5.8). Among the 16 patients who showed an increase in extent of disease during follow up, 10 were DRB1*15+ (P = 0.002; OR = 4.8). The frequency of the DRB1*13 allele was decreased in patients with UC (15% versus 28% in controls; P = 0.04; OR = 0.5). In CD, no association was observed between disease or particular clinical subgroups and any allele tested. The present study provides additional evidence for the genetic association between UC and HLA-DRB1*15, and supports recent findings that the susceptibility gene(s) for CD is not located in the HLA class II region.

Publisher

Oxford University Press (OUP)

Subject

Immunology,Immunology and Allergy

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