Association of HLA class II genes with susceptibility to Crohn's disease

Background - Published studies on the association between HLA class II genes and inflammatory bowel disease are contradictory perhaps because of the limited size and ethnic heterogeneity of the populations studied. Aim - To compare the frequencies of HLA class II genes in a large number of French patients with Crohn's disease and in an ethnically matched control group. Methods - 344 patients (196 F, 148 M, mean age 23.6 years) with Crohn's disease were molecularly genotyped for the HLA-DQB1 and DRB1 alleles. The results were compared with those for an ethnically matched control population of 488 white adults. Results - There were two significant variations of alleles at the DQB1 locus: an increase in DQB1*0501 allele frequency (χ²=10.6, corrected p value (pc)=0.01, odds ratio (OR)=1.61) and a decrease in DQB1*0602/0603 allele frequencies (χ²=8.43, pc=0.037, OR=0.66). DRB1 analysis showed associations with three allelic variations: an increase in the frequencies of DRB1*01 (χ²=12.86, pc=0.003, OR=1.75) and DRB1*07 alleles (χ²=11.18, pc=0.008, OR=1.58) and a very significant decrease in that of the DRB1*03 allele (χ²=19.7, pc=9.10^-5, OR=0.46). Conclusion - The alleles DRB1*01 and DRB1*07 are associated with susceptibility to Crohn's disease. The strong negative association between the DRB1*03 allele and Crohn's disease suggests that the HLA-DRB1*03 allele mediates 'resistance' to Crohn's disease.