Tumor necrosis factor-alpha gene polymorphism in severe and mild-moderate rheumatoid arthritis
Fabris, M.; Di Poi, E.; D'Elia, A.; Damante, G.; Sinigaglia, L.; Ferraccioli, G.
Journal of Rheumatology 29(1): 29-33
2002
ISSN/ISBN: 0315-162X PMID: 11824966 Document Number: 552031
Objective: To examine whether severe rheumatoid arthritis (RA) carries a -238 or +489 tumor necrosis factor-alpha (TNF-alpha) genotype different from mild-moderate RA. Methods: We investigated 163 patients (66 with severe disease) and 67 healthy blood donor controls. Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism. Results: Patients with severe RA (all active disease despite disease modifying antirheumatic drug combination therapy) disclosed the -238 GG genotype in 100% of cases versus 92.8% of the mild-moderates and 92.5% of controls (OR 11.7, CI 0.6-216, p=0.03). The +489 AA genotype was seen less often in patients than in controls (OR 4.2, CI 0.97-18.4, p=0.045), and the contribution to this trend appeared predominant in the anti-TNF treated subgroup. Conclusion: The -238 AG genotype was absent in severe RA; in contrast, patients with mild-moderate RA disclosed the same frequency as controls. Thus -238 GG homozygosity is associated with severe RA. The +489 AA genotype might instead protect against worse outcome in RA.