Detection of a rare CYP3A4 variant in a transplant patient characterized by a tacrolimus poor metabolizer phenotype

Pharmacogenomics. 2018 Mar;19(4):305-310. doi: 10.2217/pgs-2017-0301. Epub 2018 Feb 22.

Abstract

A validated CYP3A genotype classification system allows clustering patients into poor, intermediate and extensive metabolizer phenotypes. However, substantial overlap exists between the clusters. A rare CYP3A4 allele, named CYP3A4*20 (rs67666821), has been specifically described in the Spanish population. The authors investigated the relevance of CYP3A4*20 testing to see if the above-mentioned metabolic CYP3A classification system can be improved. In a cohort of 204 kidney transplant recipients, one male patient carrying a CYP3A4*20 allele was detected. This patient was receiving very low doses of tacrolimus to maintain therapeutic levels from day 7 onward when compared with the majority of the patients. These data suggest that this patient should be regarded as a CYP3A-poor metabolizer.

Keywords: cytochrome P450 enzymes; drug metabolism; genetic polymorphism; immunosuppression; renal transplantation; tacrolimus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alleles
  • Cytochrome P-450 CYP3A / genetics*
  • Female
  • Genotype
  • Graft Rejection / drug therapy*
  • Graft Rejection / genetics*
  • Humans
  • Immunosuppressive Agents / therapeutic use*
  • Kidney / metabolism
  • Kidney Transplantation / methods
  • Male
  • Phenotype
  • Polymorphism, Single Nucleotide / genetics*
  • Retrospective Studies
  • Tacrolimus / therapeutic use*
  • Transplant Recipients

Substances

  • Immunosuppressive Agents
  • Cytochrome P-450 CYP3A
  • CYP3A4 protein, human
  • Tacrolimus