<abstract xmlns="http://www.w3.org/1999/xhtml"><sec id="j_1905-7415.1005.512_s_001_w2aab3b7b8b1b6b1aab1c17b1Aa"><h3>Background</h3><p>Cytochrome P450 (CYP) 3A5 is a major isoform metabolizing tacrolimus. Individual variation in the metabolism may result from <italic>CYP3A5</italic> single nucleotide polymorphisms (SNPs). <italic>CYP3A5*3</italic> polymorphism is strongly associated with tacrolimus pharmacokinetic variations in 65%–85% of Asian populations. A minor polymorphism related to requirement for tacrolimus is the <italic>POR*28</italic> mutation, which increases in vivo <italic>CYP3A</italic> activity for tacrolimus. These two SNPs might affect individual maintenance dosages of tacrolimus.</p></sec><sec id="j_1905-7415.1005.512_s_002_w2aab3b7b8b1b6b1aab1c17b2Aa"><h3>Objectives</h3><p>To determine the association of <italic>CYP3A5*3</italic> and <italic>POR*28</italic> SNPs with maintenance dosage requirements for tacrolimus in Thai recipients of kidney transplants.</p></sec><sec id="j_1905-7415.1005.512_s_003_w2aab3b7b8b1b6b1aab1c17b3Aa"><h3>Methods</h3><p>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 (<italic>CYP3A5*3</italic> allele) and rs1057868 C > T (<italic>POR*28</italic> allele) were assessed. All 300 genotypes were analyzed by real-time polymerase chain reactions.</p></sec><sec id="j_1905-7415.1005.512_s_004_w2aab3b7b8b1b6b1aab1c17b4Aa"><h3>Results</h3><p>Recipients were classified into 9 groups according to possible matching genotypes. The mean dosage required for the maintenance phase was significantly higher in the <italic>CYP3A5*1</italic> 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 <italic>CYP3A5*3/*3</italic> or CYP3A5 (groups 7-9, 0.081, 0.073, and 0.069 mg/kg/day, respectively, <italic>P</italic> &lt; 0.05). When the mean dosage was compared under <italic>POR*28</italic> one or two alleles in CYP3A5 expressers, P was significantly smaller than in CYP3A5 expressers with <italic>POR*1/*1</italic>.</p></sec><sec id="j_1905-7415.1005.512_s_005_w2aab3b7b8b1b6b1aab1c17b5Aa"><h3>Conclusions</h3><p>CYP3A5 polymorphism is key to determining tacrolimus dosage requirements during the maintenance phase in kidney transplant recipients and <italic>POR*28</italic> may contribute to the interindividual variability</p></sec></abstract>

BackgroundCytochrome 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.ObjectivesTo determine the association of CYP3A5*3 and POR*28 SNPs with maintenance dosage requirements for tacrolimus in Thai recipients of kidney transplants.MethodsWe 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.ResultsRecipients 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.ConclusionsCYP3A5 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

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

Department of Pharmacology, Faculty of Medicine

Department of Medicine, Faculty of Medicine

Asian Biomedicine

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

BackgroundCytochrome P450 (CYP) 3A5 is a major isoform metabolizing tacrolimus. Individual variation in the metabolism may result from CYP3A5 single nucleotide...

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

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
CYP3A5, kidney transplantation, maintenance dose, POR, single nucleotide polymorphisms, tacrolimus

© 2016 Kreetachon Veerakikosol, Pajaree Chariyavilaskul, Natavudh Townamchai, Supeecha Wittayalertpanya

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

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

Article Category: Brief communication (Original)

Published Online: Mar 31, 2017

Page range: 483 - 490

DOI: https://doi.org/10.5372/1905-7415.1005.512

KeywordsCYP3A5, kidney transplantation, maintenance dose, POR, single nucleotide polymorphisms, tacrolimus

© 2016 Kreetachon Veerakikosol, Pajaree Chariyavilaskul, Natavudh Townamchai, Supeecha Wittayalertpanya

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Keywords
CYP3A5, kidney transplantation, maintenance dose, POR, single nucleotide polymorphisms, tacrolimus