Genotype-based tacrolimus dosing guidelines: with or without CYP3A4*22?

Aim: To test the relevance of revisiting the genotype classification based on CYP3A5*3 solely by incorporating CYP3A4*22 information.
Methods: Discriminant analysis of principal component was performed to evaluate the relevance of either the CYP3A (CYP3A5 + CYP3A4 genotypes) or CYP3A5*3 classification variables. This analysis was based on a linear combination of noncompartmental pharmacokinetics parameters.
Results: Discriminant analysis of principal component gave better results with CYP3A compared with CYP3A5*3 clustering. The centroid means of the pharmacokinetics variables were significantly different with CYP3A genotype clustering (p = 0.04) but not with CYP3A5*3 solely (p = 0.06). Canonical plots reveal a better delimitation of clusters with CYP3A genotype compared with CYP3A5*3 and the reciever operating characteristic curves confirm this better discriminative power.
Conclusion: We provide strong arguments of incorporating CYP3A4*22 genotype in practice to fine-tune the existing Clinical Phamacogenetics Implementation Consortium guidelines in the Caucasian population.