RT Journal Article
SR Electronic
T1 Folate Pathway Enzyme Gene Polymorphisms and the Efficacy and Toxicity of Methotrexate in Psoriatic Arthritis
JF The Journal of Rheumatology
JO J Rheumatol
FD The Journal of Rheumatology
SP jrheum.091311
DO 10.3899/jrheum.091311
A1 Vinod Chandran
A1 Fotios Siannis
A1 Proton Rahman
A1 Fawnda J. Pellett
A1 Vernon T. Farewell
A1 Dafna D. Gladman
YR 2010
UL http://www.jrheum.org/content/early/2010/05/12/jrheum.091311.abstract
AB Objective To determine the association between folate pathway gene polymorphisms and the effectiveness, toxicity, and drug survival of methotrexate (MTX) in psoriatic arthritis (PsA). Methods Data were obtained from a longitudinal cohort of PsA patients evaluated according to a standard protocol. Data on duration of drug therapy, dose, side effects, and reasons for discontinuation are systematically recorded. Patients treated with MTX after clinic admission who had ≥ 3 swollen joints prior to initiating MTX therapy were selected for evaluation of effectiveness. Response to MTX treatment was assessed at 6 months. Data from all patients treated in the clinic with MTX were used in evaluation of toxicity and drug survival. The following single-nucleotide polymorphisms (SNP) were measured using the Sequenom platform: MTHFR 677C>T (rs1801133), MTHFR 1298A>C (rs1801131), DHFR –473T>C (rs1650697), DHFR 35289A>G (rs1232027), and RFC 80G>A(rs1051266). Fisher’s exact test, logistic regression, and Cox proportional hazard analyses were used to determine association. Results Two hundred eighty-one patients were identified from the database. All patients were included in the analysis for side effects and drug survival, and 119 patients were included in the effectiveness analysis. The minor A allele of DHFR gene at +35289 was the only SNP demonstrating association with response to MTX therapy (OR 2.99, p = 0.02). Patients homozygous for the minor allele of MTHFR 677C/T (677TT) had more liver toxicity (Fisher exact test, p = 0.04). Conclusion Polymorphisms of the DHFR gene may be associated with MTX efficacy. MTHFR 677TT may have a relationship with MTX-induced liver toxicity in PsA.