The pharmacogenetics of Tacrolimus in Algerian kidney recipients' patients.

BACKGROUND

The aim of this study was to evaluate the impact of CYP3A5*3(rs776746), CYP3A4*1B (rs2740574), CYP3A4*22 (rs35599367) and ABCB1 3435C>T (rs1045462) on Tacrolimus (Tac) pharmacokinetics in the Algerian kidney transplant population.

MATERIALS AND

METHODS

A retrospective and prospective cross-sectional study on only adult kidney recipient patients of Algerian origin who were treated with Tacrolimus regardless of the post-transplant delay. The genotyping of the four polymorphisms was performed using the Polymerase Chain Reaction (PCR) followed by Restriction Fragment Length Polymorphism (RFLP). Exposure to Tac was expressed as the ratio between the concentration and weight-adjusted dose (C0/D).

RESULTS AND DISCUSSION: One hundred and nine kidney recipient patients were included in the study. The genotyping revealed that 67.92% of patients were homozygous mutants for the CYP3A5*3/*3, 71.29% of patients were homozygous mutants for the CYP3A4*1B/*1B, 97.25% of patients were homozygous wild-type (CYP3A4*1/*1) for the polymorphism CYP3A4*22 and 45.9% homozygous wild-type (CC) for the polymorphism ABCB1 3435C>T. Impact analysis of these polymorphisms on the dose and the C0/D ratio showed that only the CYP3A5*3 polymorphism had a significant impact on Tac dose and C0/D (P˂0.001). The CYP3A5 expressors (E) patients (genotypes *1/*1 and *1/*3) received a higher dose than non-expressors (genotype *3/*3) (0.096±0.059mg/Kg vs. 0.073±0.045mg/Kg) (P˂0.001) with an E/NE dose ratio of 1.31. The non-expressors (NE) patients (genotype *3/*3) received Tac doses less than or equal to 0.104mg/Kg (Cuttof value) (P˂0.001).

CONCLUSION

Only the CYP3A5*3 polymorphism influences the Tac pharmacokinetics in the Algerian kidney transplant population.