EVIDENCE FOR GENETIC-HETEROGENEITY IN INFLAMMATORY BOWEL-DISEASE (IBD) - HLA GENES IN THE PREDISPOSITION TO SUFFER FROM ULCERATIVE-COLITIS (UC) AND CROHNS-DISEASE (CD)

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. Th e aim of this study was to determine whether molecularly defined HLA-D R genes are associated with these diseases in a Dutch group of patient s. Fifty-nine unrelated Dutch UC patients and 89 CD patients were type d using DNA-based methods. A total of 2400 healthy local blood donors served as controls. The phenotype frequency of the HLA-DRB115 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 DRB115 alle le 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 DRB115(+) (P = 0.002; OR = 4.8). T he frequency of the DRB113 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 subgoups and any alle le tested. The present study provides additional evidence for the gene tic association between UC and HLA-DRB115, and supports recent findin gs that the susceptibility gene(s) for CD is not located in the HLA cl ass II region.