title: Association of MDR1 C3435T and RFC1 G80A polymorphisms with methotrexate toxicity and response in Jordanian rheumatoid arthritis patients.
abstract: OBJECTIVE
  Methotrexate (MTX) is the most commonly used disease-modifying antirheumatic drug for the treatment of rheumatoid arthritis (RA). Genetic polymorphisms of reduced folate carrier (RFC1 G80A) and multi-drug resistance-1 (MDR1 C3435T) might affect MTX response and/or toxicity. The aim of this study was to find out if there is an association between those polymorphisms and MTX toxicity and/or response in Jordanian RA patients.
  
  
  METHODS
  A genotyping approach was used to determine the studied polymorphisms in 159 RA patients.
  
  
  RESULTS
  There was an association between RFC1 G80A and MDR1 C3435T polymorphisms with MTX toxicity. Patients with RFC1 80GG genotype were at higher risk for gastrointestinal toxicity (p = 0.036). Patients carrying at least one MDR1 3435T variant allele were at higher risk for MTX overall toxicity (p = 0.04), especially hepatotoxicity (p = 0.028). Furthermore, the distribution of RFC1 G80A polymorphism between males and females was significantly different. The variant genotype 80AA was found to be more in males than in females (60% vs. 31%) (p = 0.011).
  
  
  CONCLUSIONS
  Our results suggest that genetic polymorphisms in methotrexate transporters affect the toxicity but not the response of MTX treatment. Further studies should be performed to have more conclusive results.
authors: Sima A
authors: SA
authors: Samara
authors: Yacoub M
authors: YM
authors: Irshaid
authors: Khader N
authors: KN
authors: Mustafa
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics* / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018501:Antirheumatic Agents / Q000009:adverse effects* / Q000378:metabolism; D018912:Arabs / Q000235:genetics*; D001172:Arthritis, Rheumatoid / Q000175:diagnosis / Q000188:drug therapy* / Q000208:ethnology / Q000235:genetics / Q000378:metabolism; D005260:Female; D005787:Gene Frequency; D006801:Humans; D007597:Jordan / Q000453:epidemiology; D008297:Male; D008727:Methotrexate / Q000009:adverse effects* / Q000378:metabolism; D008875:Middle Aged; D010597:Pharmacogenetics; D010641:Phenotype; D011110:Polymorphism, Genetic; D058978:Reduced Folate Carrier Protein / Q000235:genetics* / Q000378:metabolism; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D018501:Antirheumatic Agents; D058978:Reduced Folate Carrier Protein; C548699:SLC19A1 protein, human; D008727:Methotrexate