title: Polymorphisms of multidrug resistance gene (MDR1) and cyclosporine absorption in de novo renal transplant patients.
abstract: BACKGROUND
  Several single nucleotide polymorphisms (SNPs) in the multidrug resistance (MDR1) gene may play a role in the interindividual variation of cyclosporine A (CsA) absorption in renal transplant patients.
  
  
  METHODS
  An analysis of CsA absorption measured by the dose- and weight-adjusted 4 hr area under the time-concentration curve, AUC(0-4)/mg doseCsA/kg, was conducted on day 3 after transplantation, in 69 de novo renal transplant patients who were genotyped for MDR1 SNPs. Follow-up pharmacogenomic analysis at 1 month posttransplant was performed utilizing dose- and weight-adjusted 2-hour postdose CsA concentration (C2).
  
  
  RESULTS
  AUC(0-4)/mg doseCsA/kg was significantly higher (P=0.024) in (C/C)3435 individuals than in a grouped population of (C/T)3435 and (T/T)3435 patients on postoperative day 3. G2677T variants were not significantly correlated with CsA absorption (P=0.084). The number of C3435-G2677 haplotypes was the best predictor of CsA exposure. At 1 month posttransplant, no correlation was seen between MDR1 SNPs and CsA exposure. The frequency of wild-type variants for C3435T and G2677T were 61% and 77.6%, respectively. SNPs at G2677T and C3435T loci were found to be in linkage disequilibrium.
  
  
  CONCLUSIONS
  MDR1 polymorphisms are associated with differences in CsA exposure only in the first posttransplant week.
authors.affiliation: Department of Pathology, Queen Elizabeth II Health Sciences Centre/ Dalhousie University, Halifax, NS, Canada.
authors.forename: Clary J
authors.initials: CJ
authors.lastname: Foote
authors.forename: Wenda
authors.initials: W
authors.lastname: Greer
authors.forename: Bryce
authors.initials: B
authors.lastname: Kiberd
authors.forename: Albert
authors.initials: A
authors.lastname: Fraser
authors.forename: Joseph
authors.initials: J
authors.lastname: Lawen
authors.forename: Bjorn
authors.initials: B
authors.lastname: Nashan
authors.forename: Philip
authors.initials: P
authors.lastname: Belitsky
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000328:Adult; D016572:Cyclosporine / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D003596:Cytosine; D004247:DNA / Q000097:blood / Q000235:genetics / Q000302:isolation & purification; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics / Q000627:therapeutic use; D016030:Kidney Transplantation / Q000502:physiology*; D019520:Living Donors; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D013941:Thymine; D014019:Tissue Donors; D014184:Transplantation, Homologous
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D003596:Cytosine; D004247:DNA; D013941:Thymine