title: Analysis of associations between polymorphisms within genes coding for tumour necrosis factor (TNF)-alpha and TNF receptors and responsiveness to TNF-alpha blockers in patients with rheumatoid arthritis.
abstract: BACKGROUND
  Despite the fact that therapy with TNF-α inhibitors constitutes a breakthrough in rheumatoid arthritis management, no improvement is still achieved in approximately 30% of cases. The aim of the study was to evaluate whether single nucleotide polymorphisms (SNPs) within the TNF-α and TNF receptor encoding genes affect the efficacy of therapy with TNF-α inhibitors in patients with RA.
  
  
  METHODS
  Five SNPs within the TNF-α and TNF receptor encoding genes (TNFA: G-308A, G-238A, C-857T; TNFR1A G36A; TNFR1B T676G) were determined in 280 RA patients who had been treated with TNF-α inhibitors for at least 6 months or they stop therapy because of adverse events. The association between the relative change in DAS28 and SNP genotypes was tested by linear regression.
  
  
  RESULTS
  At week 24, low disease activity or remission was achieved by 45% of the patients. After 6 months remission of the disease or low disease activity were more frequently observed among patients homozygous for the TNFR1A 36A allele than among those who were GG homozygotes (52% vs. 34%, P=0.04). At week 24 DAS28 was significantly lower in the subgroup of patients homozygous for the TNFA-857T variant compared to the C allele carriers (P=0.045). The other polymorphisms were not found to be significantly associated with EULAR response at week 12 and 24 of the anti-TNF treatment.
  
  
  CONCLUSIONS
  Homozygosity for the TNFR1A 36A allele and the TNFA-875T variant could act as a genetic factor associated with better response to anti-TNF treatment.
authors.affiliation: Department of Rheumatology and Internal Medicine, Wroclaw Medical University, Borowska 213, 53114 Wroclaw, Poland. Electronic address: jurekswierkot0@poczta.onet.pl.
authors.forename: Jerzy
authors.initials: J
authors.lastname: Swierkot
authors.affiliation: Laboratory of Clinical Immunogenetics and Pharmacogenetics, L. Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Bogunia-Kubik
authors.affiliation: Department of Pharmacology, Wroclaw Medical University, Wroclaw, Poland; Department of Rheumatology and Internal Medicine, Wroclaw University Hospital, Wroclaw, Poland.
authors.forename: Beata
authors.initials: B
authors.lastname: Nowak
authors.affiliation: Department of Rheumatology and Internal Medicine, Wroclaw Medical University, Borowska 213, 53114 Wroclaw, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Bialowas
authors.affiliation: Department of Rheumatology and Internal Medicine, Wroclaw Medical University, Borowska 213, 53114 Wroclaw, Poland.
authors.forename: Lucyna
authors.initials: L
authors.lastname: Korman
authors.affiliation: Laboratory of Clinical Immunogenetics and Pharmacogenetics, L. Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Gebura
authors.affiliation: Clinical Department of Rheumatology and Connective Tissue Diseases, Hospital University Number 2 Jana Biziela Bydgoszcz, Wroclaw, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Kolossa
authors.affiliation: Clinical Department of Rheumatology and Connective Tissue Diseases, Hospital University Number 2 Jana Biziela Bydgoszcz, Wroclaw, Poland.
authors.forename: Slawomir
authors.initials: S
authors.lastname: Jeka
authors.affiliation: Department of Rheumatology and Internal Medicine, Wroclaw Medical University, Borowska 213, 53114 Wroclaw, Poland.
authors.forename: Piotr
authors.initials: P
authors.lastname: Wiland
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000235:genetics*; D055815:Young Adult
chemical_list: D018501:Antirheumatic Agents; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha