title: SLC19A1 80G allele as a biomarker of methotrexate-related gastrointestinal toxicity in Portuguese rheumatoid arthritis patients.
abstract: OBJECTIVE
  The aim of our study was to characterize the association of clinicopathological variables and the SLC19A1/RFC-1 G80A polymorphism in methotrexate (MTX)-related toxicity in Portuguese patients with rheumatoid arthritis.
  
  
  METHODS
  The study included 233 consecutively recruited patients with rheumatoid arthritis under MTX treatment. The SLC19A1 G80A polymorphism was evaluated by PCR-RFLP.
  
  
  RESULTS
  Statistical analysis revealed that SLC19A1 80G carriers had increased risk of gastrointestinal toxicity (odds ratio [OR]: 2.61, p = 0.019) and that regular folic acid supplementation was associated with both overall and gastrointestinal toxicity protection (OR: 0.15, p < 0.001 and OR: 0.19, p < 0.001, respectively). Multivariate analysis confirmed the association of SLC19A1 80G and regular folic acid supplementation to gastrointestinal toxicity (OR: 5.53 and 0.13, respectively). Moreover, a multivariate Cox regression model demonstrated a higher risk of earlier gastrointestinal toxicity in SLC19A1 80G carriers (hazard ratio: 3.63, p = 0.002).
  
  
  CONCLUSIONS
  SLC19A1 G80A genotyping may be a useful tool for clinicians to identify patients at higher risk for developing gastrointestinal toxicity related to MTX treatment.
authors.affiliation: CESPU, Institute of Research & Advanced Training in Health Sciences & Technologies, Department of Pharmaceutical Sciences, Higher Institute of Health Sciences (ISCS-N), Rua Central de Gandra 1317, 4585-116, Gandra PRD, Portugal and Molecular Oncology Group CI, Portuguese Institute of Oncology of Porto (IPO-Porto), Rua Dr. António Bernardino de Almeida, 4200-072, Porto, Portugal and Abel Salazar Institute for the Biomedical Sciences (ICBAS), University of Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313, Porto, Portugal.
authors.forename: Aurea
authors.initials: A
authors.lastname: Lima
authors.forename: Miguel
authors.initials: M
authors.lastname: Bernardes
authors.forename: Hugo
authors.initials: H
authors.lastname: Sousa
authors.forename: Rita
authors.initials: R
authors.lastname: Azevedo
authors.forename: Lúcia
authors.initials: L
authors.lastname: Costa
authors.forename: Francisco
authors.initials: F
authors.lastname: Ventura
authors.forename: Vítor
authors.initials: V
authors.lastname: Seabra
authors.forename: Rui
authors.initials: R
authors.lastname: Medeiros
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D018501:Antirheumatic Agents / Q000009:adverse effects / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000235:genetics*; D015415:Biomarkers / Q000378:metabolism*; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage; D041981:Gastrointestinal Tract / Q000187:drug effects* / Q000378:metabolism; D005838:Genotype; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000009:adverse effects* / Q000627:therapeutic use*; D008875:Middle Aged; D011174:Portugal; D058978:Reduced Folate Carrier Protein / Q000235:genetics*; D012189:Retrospective Studies
chemical_list: D018501:Antirheumatic Agents; D015415:Biomarkers; D058978:Reduced Folate Carrier Protein; C548699:SLC19A1 protein, human; D005492:Folic Acid; D008727:Methotrexate
keywords: SLC19A1/RFC-1 G80A polymorphism; adverse drug reactions; gastrointestinal toxicity; methotrexate; rheumatoid arthritis