To identify the association of HLA-DR4 subtypes with rheumatoid arthritis (RA) in Koreans.
Ninety five patients with RA and 118 normal control subjects were examined for HLA-DR antigens by serology. Subtypes of HLA-DR4 were determined by allele specific oligonucleotide typing.
The phenotype frequency of HLA-DR4 in RA patients was significantly greater than that in controls (60.0% versus 31.4%, odds ratio (OR) 3.28, 95% confidence interval (CI) 1.79 to 6.02 (p < 0.001)), but HLA-DR6 was decreased in RA patients (15.8% versus 32.2%, OR 0.39, 95% CI 0.19 to 0.81 (p < 0.001)). When DR4 was excluded from analysis of patients and controls, the allele frequency of DR1 was significantly increased in the patients compared with controls (11.3% versus 4.5%, OR 2.73, 95% CI 0.87 to 5.95 (p < 0.001)). Forty two of 57 DR4 positive patients (73.7%) possessed DRB1*0405, which was strongly associated with RA (44.2% of patients, versus 11.9% of controls: OR 5.88, 95% CI 2.81 to 12.47 (p < 0.001)). DRB1*0403 was not found in the patients, but was present in 8.5% of controls. Examining the third hyper-variable region at position 70-74 in the DRB1*04 chain by oligotyping, we found that 52 of 57 DR4 positive patients (91.2%) carried one of the conserved amino acid sequences QRRAA or QKRAA, known to be the epitope conferring predisposition to RA.
This study confirms that RA is strongly associated with DR4, especially with DRB1*0405, and that the presence of the inferred QRRAA sequence may be important in susceptibility to RA in Koreans.