Gene Description
CYP3A5
CYP3A5 belongs to the cytochrome P450(CYP) 3A family, which is responsible for the oxidative metabolism of tacrolimus.1 Tacrolimus is one of the most frequently prescribed immunosuppressive medications in solid organ transplantation. The drug is cleared through hepatic metabolism by CYP3A4 and CYP3A5 with biliary excretion of metabolites.1 Whereas CYP3A4 poor metabolizers are rare, loss of functional CYP3A5 is prevalent in many populations. For example, 91% of the Dutch Caucasians have the defective CYP3A5*3 allele.2 Therapeutic drug monitoring (TDM) is routinely used in tacrolimus dosing. Although CYP3A5 genotype result does not replace the TDM, it helps achieve target tacrolimus concentrations more quickly after transplantation than without the genotype results. Faster achievement of target concentration reduces the risk of graft rejection and toxicity. The Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline provides detailed recommendation on tacrolimus dosing based on CYP3A5 testing results.3
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References
- Jatinder L, et al. PharmGKB Summary: Very Important Pharmacogene Information for CYP3A5. Pharmacogenet Genom. 2012.
- Schaik RHN, et al. CYP3A5 Variant Allele Frequencies in Dutch Caucasians. Clin Chem. 2002;48(10):1668-71.
- Birdwell KA, et al. Clinical Pharmacogenetics Implementation Consortium (CPIC) Guidelines for CYP3A5 Genotype and Tacrolimus Dosing. Clin Pharmacol Ther. 2015;98(1):19-24.