HLA CLASS-II GENOTYPES ASSOCIATED WITH EARLY-ONSET PERIODONTITIS - DQB1 MOLECULE PRIMARILY CONFERS SUSCEPTIBILITY TO THE DISEASE

DNA TYPING WAS PERFORMED on 24 Japanese patients with early-onset peri odontitis (EOP) using the PCR-RFLP method to investigate an associatio n of the susceptibility to EOP with the particular HLA class II allele s (HLA-DRB1, -DQA1, and -DQB1), DRB11401, DRB1*1501, DQB1*0503, and D QB10602 were found more frequently (''susceptible'') in the EOP patie nts than in healthy controls. In contrast, DRB10405 and DQB1*0401 wer e found less frequently (''resistant'') in EOP patients, All patients carrying DQB10602 had an atypical BamHI site in the intron upstream o f the third exon of the DQB1 gene, which in our previous studies appea red to be a susceptible marker for EOP. A comparative analysis of the amino acid sequences of these susceptible and resistant HLA-DRB1 and D QB1 alleles elucidated some differences in antigen-derived peptide bin ding sites related to the susceptible or resistant alleles. Especially , DQB10503 and DQB1*0602 alleles carrying aspartic acid at position 5 7 and glycine at position 70 are increased significantly in EOP. Since amino acid residues at positions 57 and 70 on the DQB1 molecule are s upposed to be involved in antigen binding, amino acid substitutions at these positions may affect the immune responsiveness to the periodont opathic antigen. Our results suggest that the DQB1 molecule plays a cr ucial role in the pathogenesis of EOP and that the susceptibility to E OP may be determined by the binding ability between the peptide and HL A-DQ antigens.