HLA class II gene frequencies in Crohn's disease: A population based analysis in Germany

Background-Ulcerative colitis is the only known inflammatory bowel disease associated with particular HLA alleles. Whereas the association with the HLA-DRB1*15 allele has been described in several independent studies for ulcerative colitis, no contribution of HLA alleles to susceptibility in Crohn's disease has yet been shown. Aim-This study was designed to study the strength of association of HLA class II alleles as risk markers for Crohn's disease in a homogenous population in Germany. Patients-A total of 4251 randomly selected control subjects, and 162 unrelated subjects with Crohn's disease were studied. Subjects were studied for their HLA-DRB1, HLA-DQA1, and HLA-DQB1 alleles. Method-HLA DNA typing was performed after locus specific amplification with the polymerase chain reaction and reverse dot blot hybridisation. Results-The HLA-DRB1*07 was the only HLA class Ii allele found to be significantly associated with Crohn's disease (relative risk (RR)=1.9, 95% CI: 1.66 to 2.14; p=0.0001). This association remained significant after correction for the number of DRB1 alleles compared. In patients with disease onset before 35 years the RR for the disease in HLA-DRB1*07 positive subjects was found to be higher (RR=3.1, 95% CI: 2.44 to 3.76). The HLA-DRB1*03 was significantly decreased in frequency in Crohn's disease (RR=0.5, 95% CI: 0.39 to 0.61; p=0.0028). Conclusion-The HLA-DRB1*07 allele provides risk for the disease especially in patients with younger ages of onset. These data also provide indirect evidence for an immunogenetically based heterogeneity of the disease.