科研之友
微信
新浪微博
Facebook
分享链接
摘要
Background: Cytochrome P450 (CYP) 3A5 is a major isoform metabolizing tacrolimus. Individual variation in the metabolism may result from CYP3A5 single nucleotide polymorphisms (SNPs). CYP3A5*3 polymorphism is strongly associated with tacrolimus pharmacokinetic variations in 65%-85% of Asian populations. A minor polymorphism related to requirement for tacrolimus is the POR*28 mutation, which increases in vivo CYP3A activity for tacrolimus. These two SNPs might affect individual maintenance dosages of tacrolimus.
Objectives: To determine the association of CYP3A5*3 and POR*28 SNPs with maintenance dosage requirements for tacrolimus in Thai recipients of kidney transplants.
Methods: We enrolled 150 Thai recipients of kidney transplants. Clinical laboratory data were recorded 3 months after first administration of tacrolimus. Two SNPs; rs776746 A > G (CYP3A5*3 allele) and rs1057868 C > T (POR*28 allele) were assessed. All 300 genotypes were analyzed by real-time polymerase chain reactions.
Results: Recipients were classified into 9 groups according to possible matching genotypes. The mean dosage required for the maintenance phase was significantly higher in the CYP3A5*1 allele or CYP3A5 expressers (groups 1-6, 0.163, 0.167, 0.141, 0.128, 0.131, and 0.174 mg/kg/day, respectively) than those not expressing CYP3A5*33 or CYP3A5 (groups 7-9, 0.081, 0.073, and 0.069 mg/kg/day, respectively, P < 0.05). When the mean dosage was compared under POR*28 one or two alleles in CYP3A5 expressers, P was significantly smaller than in CYP3A5 expressers with POR*11.
Conclusions: CYP3A5 polymorphism is key to determining tacrolimus dosage requirements during the maintenance phase in kidney transplant recipients and POR*28 may contribute to the interindividual variability.
- 出版日期2016-10
