Combined influence of genetic and environmental factors in age of rheumatoid arthritis onset
OBJECTIVE To examine whether polymyalgia rheumatica (PMR) and late onset rheumatoid arthritis have identical or similar HLA-DRB1 genetic associations. METHODS Seventy five PMR cases without evidence of giant cell arteritis were available for study. One hundred seven RA cases were investigated, of which 62 had disease onset after age 60 years. All cases were compared with 145 ethnically matched controls. All cases and controls originated from Lugo, NW Spain. HLA-DRB1 typing was performed on DNA samples using PCR based molecular methods. RESULTS Early onset RA (< or =40 yrs) was strongly associated with DRB1*04 (DRB1*0401 and *0404). In contrast late onset RA (> or = 60 yrs) was not associated with DRB1*04 but was associated with DRB1*01. Stratification of late onset RA cases by rheumatoid factor status revealed that DRB1*01 was only increased in seropositive RA cases. Late onset seronegative RA cases exhibited increased frequency of DRB1*13/*14; this was also observed in PMR cases where coexistence of GCA had been excluded. CONCLUSION These data indicate that (1) HLA associations with RA differ with respect to age at disease onset; and (2) seronegative late onset RA and "isolated" PMR have a similar HLA-DRB1 association and may have an identical etiological basis.