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Association of CYP3A5 and POR polymorphisms with the maintenance tacrolimus dosage requirement in Thai recipients of kidney transplants

Kreetachon Veerakikosol
Kreetachon Veerakikosol
, 
Pajaree Chariyavilaskul
Pajaree Chariyavilaskul
, 
Natavudh Townamchai
Natavudh Townamchai
 and 
Supeecha Wittayalertpanya
Supeecha Wittayalertpanya
   | Mar 31, 2017
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Article Category: Brief communication (Original)
Published Online: Mar 31, 2017
Page range: 483 - 490
DOI: https://doi.org/10.5372/1905-7415.1005.512
Keywords
© 2016 Kreetachon Veerakikosol, Pajaree Chariyavilaskul, Natavudh Townamchai, Supeecha Wittayalertpanya
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

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*3/*3 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*1/*1.

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

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Language:
English
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