title: MDR1 polymorphisms and response to azathioprine therapy in patients with Crohn's disease.
abstract: BACKGROUND
  To investigate the contribution of multidrug resistance 1 (MDR1) gene pharmacogenetics (G2677T/A and C3435T) to the efficacy of azathioprine in inducing remission in patients with Crohn's disease (CD).
  
  
  METHODS
  A cohort of 327 unrelated Spanish patients with CD recruited from a single center was studied. All patients were rigorously followed up for at least 2 years (mean time, 11.5 years). A case-control analysis of MDR1 G2677T/A and C3435T SNPs and 2 loci haplotypes in 112 steroid-dependent CD patients treated with azathioprine was performed. Patients were classified on the basis of response to azathioprine.
  
  
  RESULTS
  A total 76 patients treated with azathioprine for longer than 3 months were included. Remission was achieved in 42 CD patients (55.3%). A higher frequency of the 2677TT genotype was found in nonresponders than in responders (17.65% versus 7.14%; OR = 2.8; 95% CI; 0.6-12.1; P = 0.11). Nonresponders to azathioprine were found to have a higher frequency of the 3435TT genotype than did CD patients who had achieved clinical remission (17.64% versus 4.76%; OR = 4.3; 95% CI, 0.8-22.8; P = 0.06). The 2677T/3435T haplotype was also more abundant in nonresponders (29.4% versus 20.2%), whereas the 2677G/3435C haplotype was more frequent in responders (58.3% versus 47.1%). Lack of response to azathioprine therapy in CD patients was 1.8-fold greater in carriers of the 2677T/3435T haplotype than in carriers of the 2677G/3435C haplotype (OR = 1.8; 95% CI, 0.82-3.9; P = 0.14).
  
  
  CONCLUSIONS
  The results of our study indicate higher frequencies of the 2677TT and 3435TT genotypes and the 2677T/3435T haplotype in CD patients who did not respond to azathioprine. Additional replications in independent populations would confirm the real impact of these polymorphisms in response to azathioprine therapy.
authors.affiliation: Department of Gastroenterology, Hospital Clínico San Carlos, Universidad Complutense, Madrid, Spain. jmendoza.hcsc@salud.madrid.org
authors.forename: Juan L
authors.initials: JL
authors.lastname: Mendoza
authors.forename: Elena
authors.initials: E
authors.lastname: Urcelay
authors.forename: Raquel
authors.initials: R
authors.lastname: Lana
authors.forename: M Carmen
authors.initials: MC
authors.lastname: Martín
authors.forename: Natalia
authors.initials: N
authors.lastname: López
authors.forename: Luis G
authors.initials: LG
authors.lastname: Guijarro
authors.forename: Julio A
authors.initials: JA
authors.lastname: Mayol
authors.forename: Carlos
authors.initials: C
authors.lastname: Taxonera
authors.forename: Emilio G
authors.initials: EG
authors.lastname: de la Concha
authors.forename: Amado S
authors.initials: AS
authors.lastname: Peña
authors.forename: Manuel
authors.initials: M
authors.lastname: Díaz-Rubio
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001379:Azathioprine / Q000627:therapeutic use*; D002648:Child; D003424:Crohn Disease / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D004351:Drug Resistance / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D005938:Glucocorticoids / Q000627:therapeutic use; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007422:Intestines / Q000473:pathology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012074:Remission Induction
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D005938:Glucocorticoids; D007166:Immunosuppressive Agents; D001379:Azathioprine