ベーチェット病患者のＨＬＡ‐Ｃ遺伝子解析

Abstract

HLA-C genotyping was performed for 71 Japanese patients with Behcet's disease and 74 unrelated healthy Japanese volunteers by the PCR-SSP (polymerase chain reaction-sequence specific primers) method. Based on previous studies, 19 allele specific primer sets were synthesized and used for HLA-C genotyping. The frequency of the Cw *14 allele was 52.1% in Behcet's disease patients, which was remarkably higher than the frequency of 23.0% in healthy controls (chi-square [χ2]=13.16, relative risk [R. R.]=3.6). The frequency of HLA-Cw *15 was also significantly higher in the patients with Behcet's disease (16.9% in patients vs. 6.8% in controls, χ2=3.60, R. R.=2.8). On the other hand, the frequency of HLA-Cw 0304 was significantly lower in the patient group than in the control group (7.0% in patients vs. 27.0% in controls, χ2=10.14, R. R.=0.20). The HLA-Cw 14 and Cw 15 alleles, which were significantly higher in patients, are in linkage disequilibrium with the B51 antigen and hence may have increased in association with B51. Therefore, the HLA-C allele frequencies were compared between B51-positive and-negative individuals, within each group, and no HLA-C allele showed a significant difference between the patient and control groups. Analysis, with emphasis on the linkage to HLA-Cw *14, revealed that in healthy controls, HLA-Cw *14 was associated with B44 and B51 at the frequencies of 60.0% and 35.0%, respectively. In the patient group, the rate of an association between Cw *14 and B44 was only 14.0% while an association between Cw *14 and B51 was very common (81.4%). These facts suggest that the pathogenic gene of Behcet's disease is not the HLA-C gene (HLA-Cw *14 and/or HLA-Cw *15) but the HLA-B51 gene itself or some other gene located near the HLAB locus centromeric to the HLA-C gene.