Genetic Polymorphisms and Tacrolimus Dose Requirements: Potential Implications for Ghanaian patients with End-stage renal disease

Abstract

Abstract Background: End Stage Renal Disease (ESRD) is an irreversible damage of a person’s kidney which could be fatal. However, because transplants may trigger an immune response with potential organ rejection, immunosuppressants such as tacrolimus dosing is required. Objective: To determine genetic polymorphisms in CYP3A5, CYP3A4 and MDR1 genes of Ghanaian patients with ESRD that could affect tacrolimus dose requirements. Method: This cross-sectional study comprised of 87 ESRD patients. Clinical and demographic data were collected and genomic DNA isolated. Samples were genotyped for specific SNPs using Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) and analyzed against tacrolimus dose and trough levels of transplant recipients. Results: Four, 4/87 (4.6%) patients harbored the homozygous CYP3A5*3 (6986A˃G) and 69/87 (79.31%) patients carried the homozygous CYP3A4*1B (-290A˃G), 4 of these were transplant recipients. One, 1/87 (1.15%) patient had the heterozygous MDR1_Ex21 (2677G˃T and another one 1/87 (1.15%) had the homozygous MDR1_Ex26 (3435C˃T). Four transplant recipients with the homozygous mutant CYP3A4*1B/*1B had significantly lower tacrolimus trough levels (average 5.95± 1.8ng/ml) compared with that required by a fifth transplant recipient with the heterozygous genotype (10.3ng/ml). Conclusion Most participants with ESRD harbored SNPs of CYP3A4 and CYP3A5 that could affect tacrolimus dose requirement in potential transplant recipients.