title: Association of 63/91 length polymorphism in the DHFR gene major promoter with toxicity of methotrexate in patients with rheumatoid arthritis.
abstract: Our aim was to explore the influence of 9-bp insertion/deletion and variable number of 9 bp elements (63/91) length polymorphism in noncoding interfering RNA and major promoter of DHFR gene on methotrexate (MTX) efficacy and toxicity in patients with rheumatoid arthritis (RA).
  
  
  
  Response to the MTX therapy and adverse effects were estimated in 243 RA patients genotyped for the selected polymorphism.
  
  
  
  The presence of allele 1 of analyzed polymorphism had significant protective effect against MTX toxicity (odds ratio: 0.37 [95% CI: 0.19-0.70]; p = 0.002). Results remained significant in multiple logistic regression analysis with the inclusion of disease and treatment features in the model (p = 0.03).
  
  
  
  Polymorphism 63/91 in DHFR gene promoter can modulate the onset of MTX-related adverse effects in RA patients.
authors.affiliation: Institute of Human Genetics, Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
authors.forename: Biljana
authors.initials: B
authors.lastname: Jekic
authors.affiliation: Department for International Cooperation, Center for the Promotion of Science of Republic of Serbia, Belgrade, Serbia.
authors.forename: Dubravka
authors.initials: D
authors.lastname: Vejnovic
authors.affiliation: Institute of Rheumatology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
authors.forename: Vera
authors.initials: V
authors.lastname: Milic
authors.affiliation: Institute of Human Genetics, Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
authors.forename: Nela
authors.initials: N
authors.lastname: Maksimovic
authors.affiliation: Institute of Human Genetics, Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
authors.forename: Tatjana
authors.initials: T
authors.lastname: Damnjanovic
authors.affiliation: Institute of Human Genetics, Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
authors.forename: Vera
authors.initials: V
authors.lastname: Bunjevacki
authors.affiliation: Institute of Human Genetics, Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
authors.forename: Ivana
authors.initials: I
authors.lastname: Novakovic
authors.affiliation: Institute of Human Genetics, Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
authors.forename: Ljiljana
authors.initials: L
authors.lastname: Lukovic
authors.affiliation: Institute of Rheumatology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
authors.forename: Nemanja
authors.initials: N
authors.lastname: Damjanov
authors.affiliation: Centre de Recherche, CHU Sainte-Justine, Montréal, Canada.
authors.forename: Maja
authors.initials: M
authors.lastname: Krajinovic
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000235:genetics; D005260:Female; D006801:Humans; D016015:Logistic Models; D008297:Male; D008727:Methotrexate / Q000009:adverse effects*; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics*
chemical_list: D013762:Tetrahydrofolate Dehydrogenase; D008727:Methotrexate
keywords: dihydrofolate reductase; interfering RNA; methotrexate; polymorphism; rheumatoid arthritis