title: Methotrexate pharmacokinetic genetic variants are associated with outcome in rheumatoid arthritis patients.
abstract: BACKGROUND
  Methotrexate (MTX) is the most used drug for the treatment of rheumatoid arthritis (RA) although outcome differs among patients.
  
  
  OBJECTIVE
  To evaluate whether polymorphisms in pharmacokinetic genes are associated with outcome in RA patients receiving MTX.
  
  
  METHODS
  We analyzed 28 SNPs in SLC19A1/RFC1, ABCB1, FPGS and GGH genes.
  
  
  RESULTS
  We studied 194 RA patients receiving MTX monotherapy. Two FPGS SNPs, rs10987742 and rs10106, were associated with response (p = 0.033 and p = 0.041, respectively). The FPGS rs10106 variant was also associated with MTX survival (p = 0.005) and toxicity (p = 0.021). Three ABCB1 SNPs, rs868755, rs10280623 and rs1858923, were associated with toxicity (p = 0.025, p = 0.048 and p = 0.031, respectively).
  
  
  CONCLUSIONS
  FPGS and ABCB1 genetic variants can influence the outcome in RA patients receiving MTX monotherapy.
authors.affiliation: Internal Medicine Department, Hospital de la Santa Creu i Sant Pau, Barcelona.|Faculty of Medicine, Universitat Autònoma de Barcelona (UAB), Barcelona.
authors.forename: Patricia
authors.initials: P
authors.lastname: Moya
authors.affiliation: Genetics Department, Hospital de la Santa Creu i Sant Pau, Barcelona.|U705, ISCIII Center for Biomedical Research on Rare Diseases (CIBERER), Madrid.
authors.forename: Juliana
authors.initials: J
authors.lastname: Salazar
authors.affiliation: Fundació Docència i Recerca Mutua Terrassa, Terrassa.
authors.forename: María Jesús
authors.initials: MJ
authors.lastname: Arranz
authors.affiliation: Internal Medicine Department, Hospital de la Santa Creu i Sant Pau, Barcelona.
authors.forename: César
authors.initials: C
authors.lastname: Díaz-Torné
authors.affiliation: Genetics Department, Hospital de la Santa Creu i Sant Pau, Barcelona.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: del Río
authors.affiliation: Internal Medicine Department, Hospital de la Santa Creu i Sant Pau, Barcelona.
authors.forename: Jordi
authors.initials: J
authors.lastname: Casademont
authors.affiliation: Rheumatology Department, Hospital Moisès Broggi, Sant Joan Despí, Barcelona.
authors.forename: Hèctor
authors.initials: H
authors.lastname: Corominas
authors.affiliation: Genetics Department, Hospital de la Santa Creu i Sant Pau, Barcelona.|U705, ISCIII Center for Biomedical Research on Rare Diseases (CIBERER), Madrid.
authors.forename: Montserrat
authors.initials: M
authors.lastname: Baiget
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics; D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D005260:Female; D005959:Glucosidases / Q000235:genetics; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000493:pharmacokinetics* / Q000627:therapeutic use; D008875:Middle Aged; D010453:Peptide Synthases / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D058978:Reduced Folate Carrier Protein / Q000235:genetics
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D000894:Anti-Inflammatory Agents, Non-Steroidal; D058978:Reduced Folate Carrier Protein; C548699:SLC19A1 protein, human; C028287:2-O-alpha-D-glucopyranosyl-O-beta-D-galactopyranosyl-hydroxylysine glucohydrolase; D005959:Glucosidases; D010453:Peptide Synthases; C023103:folylpolyglutamate synthetase; D008727:Methotrexate
keywords: ABCB1; FPGS; GGH; SLC19A1/RFC1; methotrexate; pharmacogenetics; rheumatoid arthritis