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. 2023 Oct;37(19-20):e24969.
doi: 10.1002/jcla.24969. Epub 2023 Oct 3.

The impact of CYP3A4 and CYP3A5 genetic variations on tacrolimus treatment of living-donor Egyptian kidney transplanted patients

Hanaa Wanas  1   2 , Mai Hamed Kamel  3 , Emad Adel William  4 , Tarek Fayad  5 , Mohamed Essmat Abdelfattah  5 , Hossein Mostafa Elbadawy  2 , Emily Samir Mikhael  3
Affiliations

The impact of CYP3A4 and CYP3A5 genetic variations on tacrolimus treatment of living-donor Egyptian kidney transplanted patients

Hanaa Wanas et al. J Clin Lab Anal. 2023 Oct.

Abstract

Background: Tacrolimus (TAC) is the mainstay of immunosuppressive regimen for kidney transplantations. Its clinical use is complex due to high inter-individual variations which can be partially attributed to genetic variations at the metabolizing enzymes CYP3A4 and CYP3A5. Two single nucleotide polymorphisms (SNPs), CYP3A4*22 and CYP3A5*3, have been reported as important causes of differences in pharmacokinetics that can affect efficacy and/or toxicity of TAC.

Objective: Investigating the effect of CYP3A4*22 and CYP3A5*3 SNPs individually and in combination on the TAC concentration in Egyptian renal recipients.

Methods: Overall, 72 Egyptian kidney transplant recipients were genotyped for CYP3A4*22 G>A and CYP3A5*3 T>C. According to the functional defect associated with CYP3A variants, patients were clustered into: poor (PM) and non-poor metabolizers (Non-PM). The impact on dose adjusted through TAC concentrations (C0) and daily doses at different time points after transplantation was evaluated.

Results: Cyp3A4*1/*22 and PM groups require significantly lower dose of TAC (mg/kg) at different time points with significantly higher concentration/dose (C0/D) ratio at day 10 in comparison to Cyp3A4*1/*1 and Non-PM groups respectively. However, CyP3A5*3 heterozygous individuals did not show any significant difference in comparison to CyP3A5*1/*3 individuals. By comparing between PM and Non-PM, the PM group had a significantly lower rate of recipients not reaching target C0 at day 14.

Conclusion: This is the first study on Egyptian population to investigate the impact of CYP3A4*22 and CYP3A5*3 SNPs individually and in combination on the TAC concentration. This study and future multicenter studies can contribute to the individualization of TAC dosing in Egyptian patients.

Keywords: C0/D ratio; CYP3A4; CYP3A5; Egyptian population; tacrolimus.

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Conflict of interest statement

The authors declare no conflict of interest.

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