HLA-DRB1*08:02 Is Associated with Bucillamine-Induced Proteinuria in Japanese Rheumatoid Arthritis Patients

BACKGROUND: Drug-induced proteinuria can occur in rheumatoid arthritis (RA) patients treated with d-penicillamine, gold salts, or bucillamine (Buc), and represents a drug hypersensitivity reaction. Striking associations of human leukocyte antigen (HLA) alleles with adverse reactions have recently been reported for many drugs. METHODS: We investigated the association of HLA class II with Buc-induced proteinuria (BI-Pro) in 485 Japanese RA patients treated with Buc, of whom 25 had developed BI-Pro. RESULTS AND CONCLUSION: This preliminary study showed a highly significant association of DRB1*08:02 with BI-Pro (P = 1.09 × 10(−6), corrected P [Pc] = 1.96 × 10(−5), odds ratio [OR] 25.17, 95% confidence interval [CI] 7.98–79.38). DQB1*04:02 was also significantly associated with increased risk of BI-Pro (P = 2.44 × 10(−5), Pc = 2.69 × 10(−4), OR 10.35, 95%CI 3.99–26.83). These findings provide useful information for promoting personalized medicine for RA.