HLA-DRB1 TYPING OF VOGT-KOYANAGI-HARADA DISEASE BY PCR-RFLP AND THE STRONG ASSOCIATION WITH DRB1-STAR-0405 AND DRB1-STAR-0410

Vogt-Koyanagi-Harada's (VKH) disease is reported to be closely associa ted with the HLA class II antigen, HLA-DR4. Serologically defined DR4 is further divided into 11 alleles by molecular HLA genotyping. Howeve r, no study of HLA-DNA typing of VKH patients has been reported. To cl arify molecular genetic mechanism underlying the susceptibility/resist ance to VKH disease, HLA-DNA typing of DR antigens (DRB1 genotyping) b y the polymerase chain reaction-restriction fragment length polymorphi sm (PCR-RFLP) method was performed. It was found that DRB10405 showed a significant association with VKH disease compared with the healthy controls (corrected p value <1X10(-5)) and that all the patients had D RB10405 and/or DRB1*0410. The specific amino acid residue shared only by these two alleles is Ser at position 57 which is located in the an tigen binding groove and may influence the immunological function as a n antigen-presenting molecule, suggesting that Ser at position 57 play s an important role in the susceptibility to VKH disease, although the possibility that the involvement of the HLA-DQ molecule, DQ4, in stro ng linkage disequilibrium with DRB10405 and DRB1*0410, cannot be excl uded.