Open AccessEffects of cytochrome P450 oxidoreductase genotypes on the pharmacokinetics of amlodipine in healthy Korean subjects
Author(s) -
Han Ji Min,
Yee Jeong,
Chung Jee Eun,
Lee Kyung Eun,
Park Kyungsoo,
Gwak Hye Sun
Publication year - 2020
Publication title -
molecular genetics and genomic medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.765
H-Index - 29
ISSN - 2324-9269
DOI - 10.1002/mgg3.1201
Subject(s) - amlodipine , genotype , single nucleotide polymorphism , cyp3a5 , genotyping , allele , cyp3a4 , pharmacokinetics , slco1b1 , pharmacology , cytochrome p450 , biology , pharmacogenetics , wild type , medicine , microbiology and biotechnology , endocrinology , genetics , gene , mutant , metabolism , blood pressure
Background The aim of this study was to investigate the effects of P450 oxidoreductase ( POR ) genetic polymorphisms on the pharmacokinetic parameters of amlodipine. Methods After a single 10‐mg dose of amlodipine administration, 25 healthy male subjects completed genotyping for 12 single nucleotide polymorphisms (SNPs) of the POR genes, cytochrome P450 (CYP)3A4 g.25343G>A (CYP3A4*1G), and CYP3A5 g.12083G>A (CYP3A5*3). Stratified analysis and in silico analysis to predict the possible effects of given variants on splicing were performed. Results The maximum blood concentration (C max ) of amlodipine in carriers of g.57332T>C and g.56551G>A SNPs of the POR gene was statistically significantly different. In addition, T‐allele carriers of g.57332T>C had a 21% higher C max than those with the CC genotype ( p = .007). Subjects who carried the wild‐type g.56551G>A allele also had a 1.12‐fold significantly higher C max than subjects with mutant‐type homozygous carriers ( p = .033). In stratified analyses, g.57332T>C was significantly associated with a 1.3‐fold increase in C max value in T‐allele carriers compared with subjects with the CC genotype in CYP3A4 and CYP3A5 expressers. POR g.57332T>C increased the score above the threshold in both ESEfinder 3.0 and HSF 3.1. Conclusion This study identified a novel SNP of the POR gene, which affected amlodipine metabolism and may reduce interindividual variation in responses to amlodipine.