Effects of polymorphisms in six candidate genes on phenytoin maintenance therapy in Han Chinese patients
Journal
Pharmacogenomics
Journal Volume
13
Journal Issue
12
Pages
1339-1349
Date Issued
2012
Author(s)
Abstract
Aim: The present study aimed to investigate the associations between variants in pharmacokinetic- and pharmacodynamic-related genes with the dosages, concentrations and concentration-dose ratios (CDRs) of phenytoin (PHT). Methods & results: Eleven genetic polymorphisms in the six candidate genes were detected in 269 epileptic patients under maintenance PHT monotherapy by real-time PCR and PCR-RFLP. Results of a bivariate analysis demonstrated that among tested polymorphisms, carriers of the variant CYP2C9*3 tended to require significantly lower maintenance PHT dosages than wild-type carriers (p < 0.0001); on the other hand, carriers of the variants CYP2C9*3 or CYP2C19*3 revealed significantly higher CDRs than wild-type carriers (p < 0.004). In a further multivariate analysis, variants in SCN1A, CYP2C9, CYP2C19 and ABCB1 genes were significantly associated with CDRs of PHT under adjustment of age, gender and epilepsy classifications (adjusted r2 = 20.07%). Conclusion: The results of present study indicated that polygenic analysis may provide useful information in PHT therapy optimization. Original submitted 3 May 2012; Revision submitted 28 June 201. ? 2012 Future Medicine Ltd.
SDGs
Other Subjects
cytochrome P450 2C19; cytochrome P450 2C9; multidrug resistance protein 1; phenytoin; sodium channel Nav1.1; sodium channel Nav1.2; ABCB1 gene; ABCC2 gene; adult; article; Chinese; controlled study; CYP2C19 gene; cyp2c9 gene; epilepsy; female; gene; genetic association; genetic polymorphism; genetic variability; heterozygote; human; maintenance therapy; major clinical study; male; real time polymerase chain reaction; restriction fragment length polymorphism; SCN1A gene; SCN2A gene; Adult; Alleles; Anticonvulsants; Aryl Hydrocarbon Hydroxylases; Asian Continental Ancestry Group; Dose-Response Relationship, Drug; Epilepsy; Female; Genotype; Humans; Male; P-Glycoprotein; Phenytoin; Polymorphism, Genetic
Type
journal article