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

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. 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. 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. HLA DNA typing was performed after locus specific amplification with the polymerase chain reaction and reverse dot blot hybridisation. 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). 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.