To analyze the association of susceptibility epitopes and alleles of HLA-DRB1 with rheumatoid arthritis (RA) in Koreans.
We performed HLA-DRB1 epitope typing in 61 patients and 82 controls using polymerase chain reaction (PCR) oligonucleotide hybridization, and HLA-DR4, DR1, and DR8 alleles were characterized by PCR single strand conformation polymorphism (SSCP).
The frequency of HLA-DR4 was significantly increased in patients with RA compared with controls (61 vs 29%; RR = 3.7, p < 0.0001). Epitope analysis revealed that susceptibility sequences in Korean patients with RA were 70QRRA74A (52 vs 21%; RR = 4.2, p < 0.0001) and 70QKRA74A (10 vs 1%; RR = 8.8, p < 0.05). The frequency of patients carrying either QRRAA or QKRAA at the 70-74 position on the HLA-DR beta 1 molecule was significantly increased compared with controls (57 vs 22%; RR = 4.8, p < 0.0001). Genotypical analysis showed that DRB1*0405 and *0401 were the DR4 alleles associated with RA in Koreans (RR = 9.4, p < 0.00005; RR = 8.8, p < 0.05, respectively). No significant differences were noted for other alleles including DRB1*0404 and DRB1*0101. QRRAA epitope typing was considered to have some diagnostic value for early RA.
Our observation indicates that a shared sequence 70QR(K)RA74A, especially in HLA-DR4 subtypes, is strongly associated with RA in the Korean population. Additionally, the importance of DRB1*0405 in the pathogenesis of RA in East Asian ethnic groups was confirmed. These data suggest that not only the specific amino acid sequences but also the whole structure of the HLA-DR beta 1 molecule are important with regard to susceptibility to RA.