Comprehensive analysis of HLA genes in Takayasu arteritis in Japan.
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, 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-B52 and B39.2 were primarily involved in the susceptibility, while the associations with DRB1 * 1502 and DPB1 * 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.
Kimura
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A
Department of Tissue Physiology, Tokyo Medical and Dental University, Japan.
Kitamura
H
H
Date
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Y
Numano
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D000483:Alleles; D000595:Amino Acid Sequence / Q000235:genetics; D005787:Gene Frequency; D008040:Genetic Linkage / Q000235:genetics; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006680:HLA Antigens / Q000235:genetics*; D015235:HLA-B Antigens / Q000235:genetics; D000949:Histocompatibility Antigens Class II / Q000235:genetics; D006650:Histocompatibility Testing; D006801:Humans; D007564:Japan; D015810:Linkage Disequilibrium; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D013625:Takayasu Arteritis / Q000235:genetics*
D005819:Genetic Markers; D006680:HLA Antigens; D015235:HLA-B Antigens; D000949:Histocompatibility Antigens Class II