Purpose: The purpose of this study was to investigate the potential impact of CYP3A4, CYP3A5, and CYP3A7 polymorphisms on the concentration and efficacy of tacrolimus in a cohort of pediatric patients with nephrotic range proteinuria.
Methods: Genetic variants including CYP3A5*3 (rs776746), CYP3A4*1G (rs2242480), rs4646437, and CYP3A7 rs2257401 and rs10211 were detected in 70 pediatric patients with nephrotic range proteinuria. The relationships of dose-adjusted trough concentration (C0) of tacrolimus with corresponding genotypes were investigated.
Results: The tacrolimus concentration in patients without CYP3A5*3 A allele was 94% higher than those with A allele (90.7 vs 54.2, P = 0.00006). The CYP3A7 rs2257401 was also associated with the concentration of tacrolimus. The C allele carriers had an obviously lower C0 than the non-carriers (62.4 vs 90.7, P = 0.001). In addition, there were significant differences in tacrolimus concentration among CYP3A7 rs10211 G carriers and non-carriers; the latter had an almost twofold C0 of the former (101.8 vs 59.6, P = 0.0004).
Conclusions: Our study demonstrated the associations between CYP3A5*3, CYP3A7 rs2257401 and rs10211, and tacrolimus concentration in pediatric patients with nephrotic range proteinuria. Children with CYP3A5*3 A, CYP3A7 rs2257401 C, and rs10211 G alleles might need a higher dose of tacrolimus.
Keywords: CYP3A5; CYP3A7; Nephrotic range proteinuria; Pediatric patients; Polymorphisms; Tacrolimus.