Pharmacogenetics of P450 CYP3A4 and CYP3A5 in the Tunisian population: Clinical application with tacrolimus

Human cytochrome P450 (CYP), particularly CYP3A4 and CYP3A5 is mainly responsible for the metabolism of several drugs including Tacrolimus. Significant interracial/interethnic variation in the expression and function of CYP3A5... [ view full abstract ]

Human cytochrome P450 (CYP), particularly CYP3A4 and CYP3A5 is mainly responsible for the metabolism of several drugs including Tacrolimus. Significant interracial/interethnic variation in the expression and function of CYP3A5 and CYP3A4 is caused by Single Nucleotide Polymorphisms (SNPs) of genes encoding these proteins. The present study investigated in Tunisian population, genetic polymorphisms of CYP3A4*1B -392A>G, CYP34*22 15389C>T and CYP3A5*3 6986A>G.

We included in this study, Tunisian healthy subjects and renal transplant recipients receiving tacrolimus. The genomic DNA was extracted from peripheral blood mononuclear cells using a salting-out procedure. CYP3A4 and CYP3A5 genotyping was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR–RFLP). The results showed that the predominant alleles in Tunisian population are wild type of CYP3A4*1B (0.87), likewise CYP3A4*22 (0.975) and CYP3A5*3 (0.82). The genotype frequencies of CYP3A4*1B, CYP3A4*22 and CYP3A5*3 were found to be 3.9%, 0.0% and 69.5%, respectively. The genotype combination of CYP3A4*1B, CYP3A4*22 and CYP3A5*3 were made as follows: extensive metabolizers (EX) when harboring: CYP3A4*1B (*1/*1, *1/*B or *1B/*1B), CYP3A4*22 (*1/*1) and CYP3A5*3 (*1/*1 or *1/*3); intermediate metabolizers (IM) : CYP3A4*1B (*1/*1 or *1/*1B), CYP3A4*22 (*1/*1 or *1/22) and CYP3A5*3 (*1/*1, *1/*3 or *3/*3) and low metabolizers (SM) : CYP3A4*1B (*1/*1); CYP3A4*22 : (*22/*22 or *1/*22) and CYP3A5*3 (*3/*3). The results showed that Tunisian population are intermediate metabolizers and most similar to Caucasians.

The genetic background of these enzymes CYP3A4*1B, CYP3A4*22 and CYP3A5*3 in this study are important in the prescription of personalized medicine