title: Tumor necrosis factor-alpha gene polymorphism in severe and mild-moderate rheumatoid arthritis.
abstract: 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, Cl 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: From the Division of Rheumatology, DPMSC, School of Medicine, University of Udine, Italy.
authors.forename: Martina
authors.initials: M
authors.lastname: Fabris
authors.forename: Emma
authors.initials: E
authors.lastname: Di Poi
authors.forename: Angela
authors.initials: A
authors.lastname: D'Elia
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Damante
authors.forename: Luigi
authors.initials: L
authors.lastname: Sinigaglia
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Ferraccioli
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000235:genetics* / Q000276:immunology / Q000503:physiopathology; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D018450:Disease Progression; D004351:Drug Resistance / Q000235:genetics / Q000276:immunology; D004359:Drug Therapy, Combination; D005260:Female; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D010641:Phenotype; D011110:Polymorphism, Genetic / Q000235:genetics*; D011237:Predictive Value of Tests; D011379:Prognosis; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics* / Q000276:immunology / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D014409:Tumor Necrosis Factor-alpha