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- Title
Effects of cytochrome P450 oxidoreductase genotypes on the pharmacokinetics of amlodipine in healthy Korean subjects.
- Authors
Han, Ji Min; Yee, Jeong; Chung, Jee Eun; Lee, Kyung Eun; Park, Kyungsoo; Gwak, Hye Sun
- Abstract
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 (Cmax) 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 Cmax 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 Cmax 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 Cmax 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.
- Subjects
CYTOCHROME P-450; SINGLE nucleotide polymorphisms; GENOTYPES; PHARMACOKINETICS; GENETIC polymorphisms
- Publication
Molecular Genetics & Genomic Medicine, 2020, Vol 8, Issue 5, p1
- ISSN
2324-9269
- Publication type
Article
- DOI
10.1002/mgg3.1201