An association analysis of HLA-DRB1 with systemic lupus erythematosus and rheumatoid arthritis in a Japanese population: effects of *09:01 allele on disease phenotypes.

Objective. To re-evaluate the roles of HLA-DRB1 alleles in susceptibility to SLE and RA and their effects on autoantibody status in large-scale Japanese cohorts. Methods. A total of 656 SLE, 2410 RA and 911 control subjects, who were all Japanese, were genotyped for HLA-DRB1 alleles using sequence-specific oligonucleotide probes. The association of alleles with disease susceptibility was tested by logistic regression analysis and by the relative predispositional effect method. The association with autoantibody status was examined by the standard χ(2) test. Results. HLA-DRB1*15:01, 09:01, 08:02 and 04:01 were significantly associated with SLE susceptibility, while shared epitope (SE) alleles and DRB109:01 were associated with RA susceptibility. The compound heterozygote of DRB109:01/15:01 conferred an increased risk for SLE compared with the homozygotes for DRB109:01 and 15:01 and was associated with earlier onset of disease, whereas the compound effect of DRB1-SE/09:01 was not clear in RA. DRB109:01 was significantly associated with the appearance of anti-Sm antibody in SLE as well as ACPA in RA, while protectively associated with anti-dsDNA antibody in SLE. No significant interaction was observed between DRB109:01 and smoking status for the appearance of ACPA, unlike that observed in SE alleles in RA. Conclusion. We identified HLA-DRB1 alleles associated with SLE and RA in a Japanese population and demonstrated a shared susceptibility of DRB109:01 between the diseases as well as its effect on autoantibody production.