HLA-DR is strongly associated with Vogt-Koyanagi-Harada disease in Mexican Mestizo patients

Purpose: To analyze the genetic background of human leukocyte antigens (HLA) of Vogt-Koyanagi-Harada (VKH) disease in Mexican Mestizo patients in order to establish whether the pathogenesis is related to the same genes or sequences described in other populations. Patients and methods: In 48 VKH patients, we performed HLA class I and class II typing using the standard microlymphocytotoxicity tests; a group of 100 nonrelated healthy subjects were analyzed for comparison. Antigen and gene frequencies were calculated for every antigen tested in patients and in controls. Results: The frequency of HLA-DR4 was significantly increased in VKH Mexican patients (x(2)Y=19.95; p=0.00001; pc=0.0002; RR=5.3; EF=0.52); a discrete increase in DR1 was also found (p=0.02). HLA-DQ8 also showed a significant association with the disease with a lower RR (3.2) and EF (0.41) than DR4. Conclusion: The strong association found with HLA-DR4 and the slight DR1 increase shown in Mexican patients with VKH suggest that a common shared sequence present in the third hypervariable region of DRB1 genes is relevant for the expression of the disease. The stronger association with DR4 than the one with DQ8 suggests that the DR locus carries the primary susceptibility genes involved in the pathogenesis of VKH.