title: The C677T polymorphism in the MTHFR gene is associated with the toxicity of methotrexate in a Spanish rheumatoid arthritis population.
abstract: OBJECTIVE
  Methotrexate (MTX) is the first-choice drug for the treatment of rheumatoid arthritis (RA) patients. However, 30% of RA patients discontinue therapy within 1 year, usually because of adverse effects. Previous studies have reported conflicting results on the association of polymorphisms in the MTHFR gene with the toxicity of MTX in RA. The aim of this study was to assess the involvement of the C677T and A1298C polymorphisms in the MTHFR gene in the toxicity of MTX in a Spanish RA population.
  
  
  METHODS
  The study included retrospectively 468 Spanish RA patients treated with MTX. Single nucleotide polymorphism (SNP) genotyping was performed using the oligonucleotide microarray technique. Allele and genotype association analyses with regard to MTX toxicity and a haplotype association test were also performed.
  
  
  RESULTS
  Eighty-four out of the 468 patients (18%) had to discontinue therapy due to adverse effects or MTX toxicity. The C677T polymorphism (rs1801133) was associated with increased MTX toxicity [odds ratio (OR) 1.42, 95% confidence interval (CI) 1.01-1.98, p = 0.0428], and the strongest association was shown in the recessive model (OR 1.95, 95% CI 1.08-3.53, p = 0.0246). The A1298C polymorphism (rs1801131) was not associated with increased MTX toxicity (OR 0.94, 95% CI 0.65-1.38, p = 0.761). A borderline significant risk haplotype was found: 677T-1298A (OR 1.40, 95% CI 1.00-1.96, p = 0.0518).
  
  
  CONCLUSIONS
  These results demonstrate that the C677T polymorphism in the MTHFR gene is associated with MTX toxicity in a Spanish RA population.
authors: Virgen de las Nieves University Hospital, Granada, Spain.
authors: R
authors: R
authors: Cáliz
authors: J
authors: J
authors: del Amo
authors: A
authors: A
authors: Balsa
authors: F
authors: F
authors: Blanco
authors: L
authors: L
authors: Silva
authors: R
authors: R
authors: Sanmarti
authors: F G
authors: FG
authors: Martínez
authors: M D
authors: MD
authors: Collado
authors: M del Carmen
authors: Mdel C
authors: Ramirez
authors: D
authors: D
authors: Tejedor
authors: M
authors: M
authors: Artieda
authors: D
authors: D
authors: Pascual-Salcedo
authors: N
authors: N
authors: Oreiro
authors: J L
authors: JL
authors: Andreu
authors: E
authors: E
authors: Graell
authors: L
authors: L
authors: Simon
authors: A
authors: A
authors: Martínez
authors: J
authors: J
authors: Mulero
mesh_terms: D000328:Adult; D018501:Antirheumatic Agents / Q000009:adverse effects*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics; D015331:Cohort Studies; D005260:Female; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000009:adverse effects*; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012189:Retrospective Studies; D013030:Spain
chemical_list: D018501:Antirheumatic Agents; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D008727:Methotrexate