Positive and negative association of HLA-DR genotypes with Japanese rheumatoid arthritis.

Objective. To clarify the relationship between the HLA-DR genotype and susceptibility to rheumatoid arthritis (RA) in Japanese patients. Methods. HLA-DR typing and DRB1* genotyping were carried out by PCR and PCR-SSCP (single stranded DNA conformation polymorphism), respectively. Results. In RA, the prevalence of HLA-DR4 was significantly higher (57.3%, p < 0.05). In particular, DRB1*0405 was predominantly higher (46. 9%, p < 0.05) and DRB1*0401 was also increased although not significantly. HLA-DR8, especially DRB1*0802, was significantly lower (1.0%, p < 0.01). RA patients homozygous for DRB1*0405 showed slightly higher values for the erythrocyte sedimentation rate, γ-globulin, and IgG, as well as positivityfor rheumatoid factor and high titers for the Waaler-Rose test, and a decrease in the albumin/globulin ratio, albumin, and hemoglobin in comparison to patients without RA susceptibility genes, although the difference for each of these parameters was not significant. Conclusion. DRB1*0405 and DRB1*0802, which are both rare alleles in Caucasians, are positively and negatively correlated, respectively, with the pathogenesis of RA in Japan.