title: Influence of ABCB1 genetic polymorphisms on cyclosporine intracellular concentration in transplant recipients.
abstract: OBJECTIVE
  The expression on lymphocytes of P-glycoprotein, an efflux transporter encoded by the ABCB1 gene, might influence cyclosporine intracellular concentration.
  
  
  METHODS
  ABCB1 genotypes, cyclosporine intracellular and blood concentrations were determined in 64 stable renal, liver or lung transplant recipients.
  
  
  RESULTS
  Cyclosporine intracellular concentration correlated moderately with blood concentration (r=0.30, P<0.00005). The ABCB1 1199A carriers presented a 1.8-fold decreased cyclosporine intracellular concentration (P=0.04), whereas the 3435T carriers presented a 1.7-fold increase (P=0.02) as well as a 1.2-fold increased blood concentration (P=0.04). In contrast, ABCB1 61A>G, 1236C>T and 2677G>T polymorphisms did not influence cyclosporine intracellular and blood concentrations.
  
  
  CONCLUSIONS
  This is the first report demonstrating that ABCB1 polymorphisms influence cyclosporine intracellular concentration. Interestingly, its influence on intracellular concentration is significantly higher than on blood concentration (P<0.002). This may therefore modulate cyclosporine immunosuppressive activity.
authors.affiliation: Unit of Biochemistry and Clinical Psychopharmacology, Centre of Psychiatric Neuroscience, Department of Psychiatry, CHUV, University of Lausanne, Hospital of Cery, Prilly, Switzerland.
authors.forename: Séverine
authors.initials: S
authors.lastname: Crettol
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Venetz
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Fontana
authors.forename: John-David
authors.initials: JD
authors.lastname: Aubert
authors.forename: Nicolas
authors.initials: N
authors.lastname: Ansermot
authors.forename: Marc
authors.initials: M
authors.lastname: Fathi
authors.forename: Manuel
authors.initials: M
authors.lastname: Pascual
authors.forename: Chin B
authors.initials: CB
authors.lastname: Eap
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000328:Adult; D000368:Aged; D016572:Cyclosporine / Q000008:administration & dosage / Q000378:metabolism*; D005260:Female; D005838:Genotype; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000378:metabolism*; D016030:Kidney Transplantation; D016031:Liver Transplantation; D016040:Lung Transplantation; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D007166:Immunosuppressive Agents; D012333:RNA, Messenger; D016572:Cyclosporine