Background: Our study aimed to investigate the pharmacogenetics of cytochrome P3A4 (CYP3A4),
CYP3A5, CYP2C8, and CYP2C19 and their influence on TAC Pharmacokinetics (PKs) in short-term renal transplant
Methods: A total of 105 renal transplant recipients were enrolled. Target Sequencing (TS) based on next-generation
sequencing technology was used to detect all exons, exon/intron boundaries, and flanking regions of CYP3A4,
CYP3A5, CYP2C8, and CYP2C19. After adjustment of Minor Allele Frequencies (MAF) and Hardy-Weinberg
Equilibrium (HWE) analysis, tagger Single-nucleotide Polymorphisms (SNPs) and haplotypes were identified. Influence
of tagger SNPs on TAC concentrations was analyzed.
Results: A total of 94 SNPs were identified in TS analysis. Nine tagger SNPs were selected, and two SNPs (rs15524
and rs4646453) were noted to be significantly associated with TAC PKs in short-term post-transplant follow-up.
Measurement time points of TAC, body mass index (BMI), usage of sirolimus, and incidence of Delayed Graft Function
(DGF) were observed to be significantly associated with TAC PKs. Three haplotypes were identified, and
rs15524-rs4646453 was found to remarkably contribute to TAC PKs. Recipients carrying H2/H2 (GG-AA) haplotype
also showed significantly high weight- and dose-adjusted TAC concentrations in posttransplant periods of 7, 14, and
30 days and 3 and 6 months.
Conclusions: Two tagger SNPs, namely, rs15524 and rs4646453, are significantly related to the variability of TAC
disposition, and TAC measurement time points, BMI, usage of sirolimus, and incidence of DGF contribute to this
influence. Recipients carrying H2/H2 (GG-AA) haplotype in rs15524–rs4646453 may require a low dosage of TAC
during 1-year follow-up posttransplant.