HLA serological and class II genotyping in sarcoidosis patients in Japan

To investigate the HLA alleles that contribute to the genetic susceptibility to sarcoidosis, HLA serological typing was performed in 75 patients with sarcoidosis and 150 controls using the standard complement-dependent microcytotoxicity method. The genomic DNAs of the 75 patients and 130 of the 150 controls were used to analyze HLA-DRB1, -DQA1, -DQB1 and -DPB1 alleles, utilizing the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Serological typing showed that the frequencies of HLA-DR52, -DR5, -DR6 and -DR8 were significantly increased in the patients compared to the controls. In PCR-RFLP genotyping, the frequencies of the DR52-associated DRB1 alleles (DRB1*11, DRB1*14), DRB1*08, DQA1*0501 and DQB1*0301 were significantly increased in the patients compared to the controls. The frequencies of the DRB1*12 alleles were also increased among the patients, but this increase was not significant. The frequencies of DRB1*0101, DQB1*0501, and DPB*0402 were significantly lower in the patients than in the controls. The significant increases in the frequencies of DQA1*0501 and DQB1*0301 could be due to the linkage disequilibrium between the DR52-associated DRB1 alleles and DQA1*0501 and DQB1*0301 alleles among the Japanese. The significantly increased frequency of the DR8 (DRB1*08) haplotype, which lacks the DRB3 gene encoding DR52 antigen, suggested that the DR5 (DRB1*11), DR6 (DRB1*14) and DR8 (DRB1*08) of the DRB1 alleles may determine the susceptibility to sarcoidosis among the Japanese.