title: Tumor necrosis factor-alpha receptor II polymorphism in patients from southern Europe with mild-moderate and severe rheumatoid arthritis.
abstract: OBJECTIVE
  To define the frequency of the exon 6 tumor necrosis factor-alpha (TNF-alpha) receptor II (TNFRII) gene polymorphism in severe and mild-moderate rheumatoid arthritis (RA) and its possible influence on anti-TNF-alpha treatment responsiveness.
  
  
  METHODS
  Two cohorts of patients with RA, the first (n = 97) defined as methotrexate responders (MTX-R) with mild-moderate synovitis, and the second (n = 78) defined as nonresponders to combination therapy and receiving anti-TNF-alpha treatment because of their severe and aggressive disease (TNF-T), were studied retrospectively and compared to age, sex, and ethnically matched controls (n = 84). In the prospective study, 66 patients with severe RA were followed over the first 6 months of anti-TNF-alpha therapy and their response was examined according to genotype.
  
  
  RESULTS
  We observed a trend towards an increased frequency of the GG genotype in patients with severe RA (6.4%) in comparison with patients with mild-moderate disease (3.1%) and controls (1.2%). When looking at the response to anti-TNF-alpha therapy, we observed that after 12 weeks of treatment, 37.8% of the TT versus 10.7% of the TG/GG patients passed from high to medium-low disease activity (p = 0.03).
  
  
  CONCLUSIONS
  In our cohorts of patients selected by response to the conventional therapy and by disease severity, our preliminary study results showed a trend towards a higher prevalence of the GG genotype for the exon 6 TNFRII polymorphism in the less responsive patients with more aggressive disease. We also found a lower degree of response to anti-TNF-alpha treatments in patients carrying the G allele.
authors.affiliation: Division of Rheumatology, DPMSC School of Medicine. University of Udine, Italy.
authors.forename: Martina
authors.initials: M
authors.lastname: Fabris
authors.forename: Barbara
authors.initials: B
authors.lastname: Tolusso
authors.forename: Emma
authors.initials: E
authors.lastname: Di Poi
authors.forename: Roberta
authors.initials: R
authors.lastname: Assaloni
authors.forename: Luigi
authors.initials: L
authors.lastname: Sinigaglia
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Ferraccioli
mesh_terms: D000328:Adult; D017677:Age Distribution; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000235:genetics*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000453:epidemiology / Q000235:genetics*; D016022:Case-Control Studies; D004359:Drug Therapy, Combination; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D015994:Incidence; D007558:Italy / Q000453:epidemiology; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use*; D008875:Middle Aged; D016017:Odds Ratio; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic; D011241:Prednisone / Q000627:therapeutic use*; D011336:Probability; D011379:Prognosis; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics*; D047889:Receptors, Tumor Necrosis Factor, Type II; D012016:Reference Values; D012189:Retrospective Studies; D012307:Risk Factors; D012720:Severity of Illness Index; D012723:Sex; D017678:Sex Distribution; D016896:Treatment Outcome
chemical_list: D015703:Antigens, CD; D018124:Receptors, Tumor Necrosis Factor; D047889:Receptors, Tumor Necrosis Factor, Type II; D011241:Prednisone; D008727:Methotrexate