HLA-A and DPB1 loci confer susceptibility to Grave's disease

To investigate HLA-linked genetic factors involved in the pathogenesis of Grave's disease, 76 patients and 317 healthy controls in the Japanese population were examined for HLA-A, B, C, DR, and DQ specificities by serologic typing and for HLA-DPB1 alleles by DNA typing by using the PCR-SSOP method. The frequencies of HLA-A2, B46, Cw11, and DPB1^*0501 were increased and those of HLA-A24, B7, Bw52, and DR1 were decreased in the patients. The increased frequencies of HLA-A2 and DPB1^*0501 in the patients were statistically significant when the corrected value (p_c) was applied (p_c < 0.02 and p_c < 0.002, respectively). ORs for a risk to develop the disease were calculated among individuals positive for DPB1^*0501 and/or HLA-A2, and the highest OR (10.5) was observed in individuals possessed both DPB1^*0501 and HLA-A2. This observation suggests a synergic involvement of a HLA class II allele (DPB1^*0501) and an HLA class I allele (HLA-A2) in the pathogenesis of Grave's disease.