Comprehensive analysis of HLA genes in Takayasu arteritis in Japan

Abstract To identify an HLA-linked susceptibility gene to Takayasu's arteritis, comprehensive analysis of HLA genes was performed. By serologic HLA typing, positive associations of Takayasu's arteritis with HLA-B52 and B39 were observed. The DNA typing of HLA-B gene and class II genes (DRB1, DQA1, DQB1, DPB1) showed positive associations of the disease with HLA-B52, B39.2, DRB1 * 1502 and DPB1 * 0901, confirming in part the serologic observations. Comparison of odds ratio for the risk of disease revealed that HLA-BS2 and B39.2 were primarily involved in the susceptibility, while the associations with DRBI * 1502 and DPBI * 0901 were suggested to reflect a strong linkage disequilibrium of these class II alleles with HLA-B52 in the Japanese population. Sequencing analyses of HLA-B52 and B39.2 from patients confirmed that they were B * 5201 and B * 3902, respectively. Comparison of amino acid sequences of these disease-associated HLA-B alleles identified critical amino acid residues of the HLA-B molecule, Glu and Ser at 63rd and 67th positions, respectively, which may determine the susceptibility to Takayasu's arteritis via binding and presenting a yet unknown disease-related antigen.