title: Association of DHODH haplotype variants and response to leflunomide treatment in rheumatoid arthritis.
abstract: OBJECTIVE
  Leflunomide is a disease-modifying antirheumatic drug used in the treatment of rheumatoid arthritis. Not all patients respond to leflunomide and, as it has potentially serious side effects, targeting only those most likely to benefit would address a clinical need. We aimed to determine whether variations in the gene encoding DHODH, the molecular target of leflunomide, might include biomarkers that could be used to rationalize provision of this drug.
  
  
  METHODS
  We analyzed six haplotype-tagging SNPs in DHODH in 56 patients with rheumatoid arthritis treated with leflunomide. Clinical response was determined by assessing the change in 28 joint disease activity score over the first 3 months of treatment.
  
  
  CONCLUSIONS
  Carriage of a six-marker DHODH haplotype was associated with a reduced treatment response (p = 0.008). This suggests that a functional variant in strong linkage disequilibrium with this haplotype may predispose to reduced leflunomide efficacy.
authors.affiliation: University of South Australia, Sansom Institute for Health Research & School of Pharmacy & Medical Sciences, Frome Road, GPO Box 2471, Adelaide, South Australia, 5000, Australia.
authors.forename: Catherine
authors.initials: C
authors.lastname: O'Doherty
authors.forename: Matthew
authors.initials: M
authors.lastname: Schnabl
authors.forename: Llewellyn
authors.initials: L
authors.lastname: Spargo
authors.forename: Leslie G
authors.initials: LG
authors.lastname: Cleland
authors.forename: Michael
authors.initials: M
authors.lastname: James
authors.forename: Susanna M
authors.initials: SM
authors.lastname: Proudman
authors.forename: Michael D
authors.initials: MD
authors.lastname: Wiese
mesh_terms: D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics*; D000090722:Dihydroorotate Dehydrogenase; D005260:Female; D006239:Haplotypes; D006801:Humans; D007555:Isoxazoles / Q000627:therapeutic use*; D000077339:Leflunomide; D008297:Male; D008875:Middle Aged; D044925:Oxidoreductases Acting on CH-CH Group Donors / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D055815:Young Adult
chemical_list: D018501:Antirheumatic Agents; D000090722:Dihydroorotate Dehydrogenase; D007555:Isoxazoles; D044925:Oxidoreductases Acting on CH-CH Group Donors; D000077339:Leflunomide