Predominance of HLA-DRB1*0405 in Korean patients with rheumatoid arthritis

Abstract

Objective-To identify the association of HLA-DR4 subtypes with rheumatoid arthritis (RA) in Koreans. Methods-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. Results-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 ofpatients and controls, the allele frequency of DRI 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 (73.70/6) 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 hypervariable 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. Conclusion-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.