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Type: Journal article
Title: Association of DHODH haplotype variants and response to leflunomide treatment in rheumatoid arthritis
Author: O'Doherty, C.
Schnabl, M.
Spargo, L.
Cleland, L.
James, M.
Proudman, S.
Wiese, M.
Citation: Pharmagenomics, 2012; 13(12):1427-1434
Publisher: Future Medicine Ltd
Issue Date: 2012
ISSN: 1462-2416
Statement of
Catherine O’Doherty, Matthew Schnabl, Llewellyn Spargo, Leslie G Cleland, Michael James, Susanna M Proudman & Michael D Wiese
Abstract: AIM: 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. MATERIALS & 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. RESULTS & CONCLUSION: 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.
Keywords: DHODH; leflunomide; pharmacogenomics; polymorphism; response; rheumatoid arthritis
Rights: © 2012 Future Medicine Ltd
RMID: 0020122280
DOI: 10.2217/pgs.12.118
Appears in Collections:Medicine publications
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