Associations of CYP3A4/5 and POR Polymorphisms with Tacrolimus Concentrations in Chinese Adult Heart Transplant Recipients / 中国药学杂志

ABSTRACT

OBJECTIVE: To investigate associations between CYP3A4/5 and POR single nucleotide polymorphisms(SNPs)and tacrolimus dose-corrected concentrations(ρ0/D) in Chinese adult heart transplant recipients, providing individualized dose-adjustment for this population. METHODS: A total of 90 Chinese adult heart transplant recipients in the early stage were enrolled. CYP3A4*1G G>A(rs2242480) genotype was assessed by pyrophosphate sequencing. CYP3A5*3 A>G(rs776746) and POR*28 C>T(rs1057868) genotype were determined by Sanger sequencing. Tacrolimus trough concentration(ρ0) was evaluated by enzyme multiplied immunoassay technique(EMIT). Associations between genotypes and ρ0/D as well as time and dose to get the target range were completely analyzed. RESULTS: Allele frequencies of all the evaluated SNPs were consistent with Hardy-Weinberg equilibrium (P>0.05). The ρ0/D in CYP3A5*3/*3 carriers was considerably higher than that in *1/*1and *1/*3 carriers. Moreover, time to get the target range was significantly shortened and required dosage was also significantly reduced in CYP3A5*3/*3 carriers. The ρ0/D in CYP3A4*1/*1G carriers was remarkably decreased in comparison with the wild type. After stratification by CYP3A5*3 genotypes, no associations were observed between CYP3A4*1G and POR*28 genotypes and tacrolimus ρ0/D. POR*28 was not related to ρ0/D, but significantly prolonged time to target range. CONCLUSION: This study demonstrats that CYP3A4*1G and CYP3A5*3 polymorphisms are associated with tacrolimus concentrations, the test of these genotypes before transplantation may be useful for individualized medicine of tacrolimus.