Different gene loci within the HLA-DR and TNF regions are independently associated with susceptibility and severity in Spanish rheumatoid arthritis patients

The aim of this study was to investigate whether polymorphisms in the tumor necrosis factor (TNF) and HLA-DRB1 gene regions are independently associat ed with rheumatoid arthritis (RA) in a population from Lugo region of north western Spain. WI patients (n = 179) attending hospital outpatient clinics in Lugo, northwestern Spain and matched controls (n = 145) were recruited. RA susceptibility in this population was pre dominantly associated with DRB 1*0401, while erosive disease was associated with HLA-DRB1*0101 and DRB1*04 , The increase in DRB1*04 was accounted for by an increase in DRB1*0404 and *0405 but not *0401 frequencies. In contrast, *0401 frequency was signific antly increased in seropositive patients. The rheumatoid arthiritis shared epitope (SE) was associated with increased risk for seropositive and erosiv e disease and this appeared to operate in a dose-dependent manner, Logistic regression analyses revealed that the TNF microsatellite markers TNFcl and b3 were associated with RA independently of DRB1*04 and the SE. Carriage o f a TNF cl allele provided an increased risk of RA in SE-negative and SE-he terozygous individuals, TNFcl and TNFb3 were not associated with erosive or seropositive disease. In contrast, TNF a2 was significantly associated wit h erosive disease which was independent of DRB1*04 and the SE. Further stud ies will be needed to establish why (TNFcl) polymorphism seemingly associat ed with low TNF alpha production, is a risk factor for WI.