The effect of CYP3A5 polymorphism on cyclosporine plasma level in Egyptian renal transplant recipients

Abstract

Cyclosporine (CsA) and tacrolimus are immunosuppressants used for the prevention of rejection of transplanted organs. The genes encoding cytochrome (CYP) P450 enzymes, CYP3A4, and CYP3A5 are the main ones involved in the pharmacokinetics of calcinurin inhibitors (CNI). Several single nucleotide polymorphisms were identified in these genes such as CYP3A5*3 (6986A>G). The association of the CYP3A5*3/*3 genotype with decreased clearance of its substrates was reported among different ethnic populations. This study aims to evaluate the effect of CYP3A5*3 polymorphism on CsA plasma levels in Egyptian renal transplant patients at the first week and first month of transplantation. A total of 44 renal transplant recipients receiving CsA were genotyped for CYP3A5*3 polymorphism. The C0 and C2 of CsA were measured and their relationships with CYP3A5*3 genotypes were investigated. CYP3A5*3 allele was present in six patients and the CsA level didn’t differ significantly between the CYP3A5*3 the CYP3A5*1 allele carriers at the first week and the first month post transplantation. Large-scale studies with the involvement of multiple genetic markers claimed to affect the CsA pharmacokinetics are highly recommended to elucidate their pharmacogenetic role in renal transplant patients.