Influence of ABCB1 genetic polymorphisms on cyclosporine intracellular concentration in transplant recipients

Pharmacogenet Genomics. 2008 Apr;18(4):307-15. doi: 10.1097/FPC.0b013e3282f7046f.

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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics*
  • Adult
  • Aged
  • Cyclosporine / administration & dosage
  • Cyclosporine / metabolism*
  • Female
  • Genotype
  • Humans
  • Immunosuppressive Agents / administration & dosage
  • Immunosuppressive Agents / metabolism*
  • Kidney Transplantation*
  • Liver Transplantation*
  • Lung Transplantation*
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide / genetics*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • ABCB1 protein, human
  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Immunosuppressive Agents
  • RNA, Messenger
  • Cyclosporine