Human leucocyte antigens and Japanese patients with polymyalgia rheumatica: the protective effect ofDRB1*09:01

Abstract

ObjectiveThe 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.MethodsGenotyping ofDRB1andDQB1was performed in Japanese PMR patients (n=270) and controls (n=413). Associations between allele carrier and genotype frequencies were determined for PMR.ResultsDRB1*04:05was associated with a predisposition to PMR (p=0.0006,Pc=0.0193, OR 1.85, 95% CI 1.31 to 2.62).DRB1*09:01was 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*03:03(p=0.0010,Pc=0.0140, OR 0.52, 95% CI 0.35 to 0.77) was associated with protection against PMR andDQB1*04:01(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 forDRB1*09:01andDQB1*03:03, but not forDRB1*04:05,SE orDQB1*04:01. Haplotype and logistic regression analyses suggested a protective effect forDRB1*09:01.ConclusionThis study is the first to demonstrate predisposing associations ofDRB1*04:05,SE, andDQB1*04:01, and protective associations ofDRB1*09:01andDQB1*03:03with PMR in Japanese patients. Our data indicateHLAhas predisposing and protective effects on the pathogenesis of PMR.