Article Text

PDF
Dihydroorotate dehydrogenase polymorphism influences the toxicity of leflunomide treatment in patients with rheumatoid arthritis
  1. P Bohanec Grabar1,
  2. B Rozman2,
  3. D Logar2,
  4. S Praprotnik2,
  5. V Dolžan1
  1. 1
    Institute of Biochemistry, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia
  2. 2
    Department of Rheumatology, University Medical Centre Ljubljana, Ljubljana, Slovenia
  1. Dr V Dolžan, Institute of Biochemistry, Faculty of Medicine, University of Ljubljana, Vrazov trg 2, 1000 Ljubljana, Slovenia, vita.dolzan{at}mf.uni-lj.si

Statistics from Altmetric.com

Leflunomide is a disease-modifying antirheumatic drug used for the treatment of rheumatoid arthritis (RA). Its safety and efficacy was initially described in 1995.1 In vitro studies have demonstrated that CYP1A2 is one of the main leflunomide metabolising enzymes.2 We have previously shown that polymorphisms in CYP1A2 may be associated with leflunomide toxicity in patients with RA.3 As leflunomide metabolite directly inhibits dihydroorotate dehydrogenase (DHODH),4 we investigated whether the DHODH A40C polymorphism (rs3213422) that causes substitution of Lys7 to Gln is associated with leflunomide toxicity.

Our study included 105 patients with RA, of whom 62 tolerated the leflunomide treatment well (group A), while 43 patients discontinued …

View Full Text

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.