title: Influence of Promoter Polymorphisms of the TNF-α (-308G/A) and IL-6 (-174G/C) Genes on Therapeutic Response to Etanercept in Rheumatoid Arthritis.
abstract: BACKGROUND
  The study was undertaken to assess the influence of functional -308G/A TNF-α (rs 1800629) and -174G/C IL-6 (rs1800795) promoter polymorphisms on the therapeutic response to etanercept, a TNF-α blocker, in patients with rheumatoid arthritis (RA).
  
  
  METHODS
  Seventy-three patients suffering from active RA were studied, at baseline and 6 and 12 months after therapy. The therapeutic response was estimated according to the European League Against Rheumatism response criteria. Patients were genotyped for -308G/A TNF-α and -174G/C IL-6 polymorphisms by the PCR-RFLP method, and the influence of genotype on etanercept response was assessed.
  
  
  RESULTS
  No difference in the percentage of responders (patients who had DAS28 improvement > 1.2) between patients with the TNF-α-308GG and GA and AA genotype was detected after 6 and 12 months of treatment. After 12 months of treatment the percentage of responders was significantly increased in patients with the IL-6 -174GG genotype compared with those with the GC or CC genotype (p=0.006 by Chi-square test). Evaluation of the patients according to their combined IL-6/TNF-α genotypes showed that patients with the IL-6 -174GG / TNF-α-308GG genotype were more frequent among the responders compared to those with other combined genotypes (p=0.022 by Chi-square test). More precisely, all patients with the combined IL-6 -174GG / TNF-α-308GG genotype were responders after 12 months of etanercept treatment.
  
  
  CONCLUSIONS
  The study suggests that patients who are genetically low TNF-α and IL-6 producers are the best responders to etanercept therapy.
authors.affiliation: Department of Microbiology and Immunology, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia.
authors.forename: Ivan
authors.initials: I
authors.lastname: Jančić
authors.affiliation: Institute of Rheumatology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
authors.forename: Mirjana
authors.initials: M
authors.lastname: Šefik-Bukilica
authors.affiliation: Institute of Rheumatology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
authors.forename: Slađana
authors.initials: S
authors.lastname: Živojinović
authors.affiliation: Institute of Rheumatology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
authors.forename: Nemanja
authors.initials: N
authors.lastname: Damjanov
authors.affiliation: Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade, Serbia.
authors.forename: Vesna
authors.initials: V
authors.lastname: Spasovski
authors.affiliation: Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade, Serbia.
authors.forename: Nikola
authors.initials: N
authors.lastname: Kotur
authors.affiliation: Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade, Serbia.
authors.forename: Kristel
authors.initials: K
authors.lastname: Klaassen
authors.affiliation: Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade, Serbia.
authors.forename: Sonja
authors.initials: S
authors.lastname: Pavlović
authors.affiliation: Department of Microbiology and Immunology, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia.
authors.forename: Biljana
authors.initials: B
authors.lastname: Bufan
authors.affiliation: Department of Microbiology and Immunology, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia.
authors.forename: Nevena
authors.initials: N
authors.lastname: Arsenović-Ranin
keywords: -174G/C IL-6 gene polymorphism; -308G/A TNF-α gene polymorphism; etanercept; pharmacogenetics; rheumatoid arthritis