Human leucocyte antigens and Japanese patients with polymyalgia rheumatica: the protective effect of DRB1*09:01.

ABSTRACT

OBJECTIVE: The hallmarks of the chronic inflammatory disease polymyalgia rheumatica (PMR) include pain, and morning stiffness in areas of the neck, shoulder and pelvic girdle. The human leucocyte antigen (HLA) gene was reported to be an important risk factor for PMR, but it has not been analysed precisely, especially in populations other than Europeans. METHODS: Genotyping of DRB1 and DQB1 was performed in Japanese PMR patients (n=270) and controls (n=413). Associations between allele carrier and genotype frequencies were determined for PMR. RESULTS: DRB1*0405 was associated with a predisposition to PMR (p=0.0006, Pc=0.0193, OR 1.85, 95% CI 1.31 to 2.62). DRB1*0901 was associated with protection against PMR (p=1.46×10-5, Pc=0.0004, OR 0.40, 95% CI 0.26 to 0.61). A shared epitope (SE) associated with PMR (p=3.07×10-6, OR 2.11, 95% CI 1.54 to 2.88). DQB1*0303 (p=0.0010, Pc=0.0140, OR 0.52, 95% CI 0.35 to 0.77) was associated with protection against PMR and DQB1*0401 (p=0.0009, Pc=0.0140, OR 1.82, 95% CI 1.28 to 2.58) was associated with predisposition to PMR. A gene dosage effect was observed for DRB1*0901 and DQB1*0303, but not for DRB1*0405, SE or DQB1*0401. Haplotype and logistic regression analyses suggested a protective effect for DRB1*0901. CONCLUSION: This study is the first to demonstrate predisposing associations of DRB1*0405, SE, and DQB1*0401, and protective associations of DRB1*0901 and DQB1*0303 with PMR in Japanese patients. Our data indicate HLA has predisposing and protective effects on the pathogenesis of PMR.