Tacrolimus pharmacogenetics: the CYP3A5*1 allele predicts low dose-normalized tacrolimus blood concentrations in whites and South Asians

Transplantation. 2005 Feb 27;79(4):499-502. doi: 10.1097/01.tp.0000151766.73249.12.

Abstract

Previously, we demonstrated that the dose-normalized tacrolimus blood concentration after renal transplantation was associated with a single nucleotide polymorphism (SNP) in the CYP3AP1 gene, probably through linkage with an SNP in the CYP3A5 gene. Individuals with at least one CYP3A5*1 allele synthesize CYP3A5 and CYP3A5*3/*3 homozygotes do not. We now present results with direct typing of the CYP3A5 genotype for this group of 180 kidney-only transplant recipients from a single center. South Asian and white patients with at least one CYP3A5*1 allele achieved twofold lower dose-normalized tacrolimus blood concentrations compared with CYP3A5*3/*3 homozygotes, confirming our previous findings for the CYP3AP1 SNP. There was a significant delay in achieving target blood concentrations in those with at least one CYP3A5*1 allele. Determination of the CYP3A5*1/*3 genotype could be used to predict the tacrolimus dose requirement and, given incomplete linkage, would be better than determination of the CYP3AP1 genotype.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Alleles
  • Asian Continental Ancestry Group
  • Cytochrome P-450 CYP3A
  • Cytochrome P-450 Enzyme System / genetics*
  • European Continental Ancestry Group
  • Female
  • Genotype
  • Humans
  • Immunosuppressive Agents / blood*
  • Kidney Transplantation*
  • Male
  • Middle Aged
  • Pharmacogenetics
  • Polymorphism, Single Nucleotide*
  • Tacrolimus / blood*

Substances

  • Immunosuppressive Agents
  • Cytochrome P-450 Enzyme System
  • CYP3A protein, human
  • CYP3A5 protein, human
  • Cytochrome P-450 CYP3A
  • Tacrolimus