Introduction: At present time tacrolimus is a main immunosuppressant drug in solid organ transplantation. Its therapeutic range is narrow and pharmacokinetic properties vary among patients. CYP3A5 is the most effective single-nucleotide polymorphism (SNPs) that plays a significant role in the pharmacokinetics of tacrolimus (TAC).
The aim of this study was to evaluate the influence of CYP3A5 (G6986A, rs776746) gene polymorphism on tacrolimus variability in adult heart transplant recipients.
Methods: The study included 168 heart transplant recipients (147 men; 47±13 years). CYP3A5 [*1/*1 (expresser), *1/*3 (expresser); *3/*3 (non-expresser)] gene polymorphisms were determined by allele-specific polymerase chain reaction (Lytech, Russia). The trough concentration (C0) of TAC was measured by Architect (Abbott, USA) one month and one year after heart transplantation (HTx).
Results: The CYP3A5*1/*1, CYP3A5*1/*3 and CYP3A5*3/*3 allelic frequencies were 1,2%, 10,1% and 88,7%, respectively. TAC dose was significantly lower in *3/*3 genotype than in *1/*1, *1/*3 genotypes at the 1st months after HTx, p ≤ 0.03. The trough concentration of TAC was statistically higher in the *3/*3 genotype than in *1/*1, *1/*3 genotypes at the 1st months after HTx and was 10.0 [8.0; 12.9] ng/ml vs 8.0 [5.7; 8.4] ng/ml (p ≤ 0.003). After 12 months, the concentration of TAC (C0) did not differ depending on the genotype and was 8.3 [6.8: 9.8]ng/ml vs 8.4 [6.4; 10.6] ng/ml, but TAC dose was significantly higher in *1/*1, *1/*3 genotypes than in *3/*3 genotype (p ≤ 0.01).
Conclusions: CYP3A5 genetic polymorphisms affected the TAC concentration and dose requirements in heart transplant recipients. Screening for this single nucleotide polymorphism before the heart transplantation might be helpful for the selection of adequate initial daily dose of TAC.