Impact of CYP3A5 and MDR-1 gene polymorphisms on the dose and level of tacrolimus among living-donor liver transplanted patients: single center experience

Biomarkers. 2016;21(4):335-41. doi: 10.3109/1354750X.2016.1139002. Epub 2016 Feb 9.

Abstract

Aim of work: To assess the impact of Cytochrome P450 3A5 (CYP3A5) and multidrug resistance-1 gene (MDR-1) single nucleotide polymorphisms on the dose and blood level of tacrolimus among liver transplanted patients.

Patients and methods: We enrolled a prospective study of 41 liver transplanted patients. Dose-adjusted trough blood concentration (C/D ratio) was calculated. Polymerase chain reaction-restriction fragment length polymorphism followed by sequencing was done for genotyping of CYP3A5*3 (6986A > G).

Results: At 1 week, 1 and 3 months C/D ratio were significantly lower in CYP3A5 expressers *1/*1 patients compared to non-expressers *3/*3.

Conclusion: CYP3A5 (6986A > G) genotype, rather than MDR-1 (2677G > A/T) variant, has an impact on tacrolimus pharmacokinetics.

Keywords: Cytochrome P450; liver transplantation; multidrug resistance-1; tacrolimus.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B / genetics
  • Cytochrome P-450 CYP3A / genetics*
  • Dose-Response Relationship, Drug
  • Electrophoresis, Agar Gel
  • Humans
  • Immunosuppressive Agents / therapeutic use*
  • Liver Transplantation*
  • Living Donors*
  • Polymerase Chain Reaction
  • Polymorphism, Genetic*
  • Tacrolimus / therapeutic use*

Substances

  • ABCB1 protein, human
  • ATP Binding Cassette Transporter, Subfamily B
  • Immunosuppressive Agents
  • Cytochrome P-450 CYP3A
  • Tacrolimus