An identification and functional evaluation of a novel CYP2C9 variant CYP2C9*62.
Aged, 80 and over
Alleles
Animals
Cytochrome P-450 CYP2C9
/ genetics
Diclofenac
/ metabolism
Enzyme Assays
Humans
Kinetics
Losartan
/ metabolism
Male
Microsomes
/ metabolism
Point Mutation
Polymorphism, Genetic
Recombinant Proteins
/ genetics
Spodoptera
/ genetics
Tolbutamide
/ metabolism
Vitamin K Epoxide Reductases
/ genetics
Warfarin
/ pharmacology
Allelic variant
CYP2C9
Drug metabolism
Functional analysis in vitro
Journal
Chemico-biological interactions
ISSN: 1872-7786
Titre abrégé: Chem Biol Interact
Pays: Ireland
ID NLM: 0227276
Informations de publication
Date de publication:
25 Aug 2020
25 Aug 2020
Historique:
received:
31
03
2020
accepted:
08
06
2020
pubmed:
13
6
2020
medline:
1
9
2020
entrez:
13
6
2020
Statut:
ppublish
Résumé
Warfarin is the most commonly used anticoagulant in the clinical treatment of thromboembolic diseases. The dose of warfarin varies significantly within populations, and the dose is closely related to the genetic polymorphisms of the CYP2C9 and VKORC1 genes. In this study, a new CYP2C9 nonsynonymous mutation (8576C > T) was detected after the genetic screening of 162 patients took warfarin. This mutation, named as the new allele CYP2C9*62, can result in an arginine to cysteine amino acid substitution at position 125 of the CYP2C9 protein (R125C). When expressed in insect cells, the protein expression of CYP2C9.62 was significantly lower than that of the wild-type, and its metabolic activity was also significantly decreased after the addition of three typical CYP2C9 probe drugs, suggesting that the new mutant can dramatically affect the metabolism of CYP2C9 drugs in vitro.
Identifiants
pubmed: 32531309
pii: S0009-2797(20)30465-8
doi: 10.1016/j.cbi.2020.109168
pii:
doi:
Substances chimiques
Recombinant Proteins
0
Diclofenac
144O8QL0L1
Warfarin
5Q7ZVV76EI
Tolbutamide
982XCM1FOI
CYP2C9 protein, human
EC 1.14.13.-
Cytochrome P-450 CYP2C9
EC 1.14.13.-
VKORC1 protein, human
EC 1.17.4.4
Vitamin K Epoxide Reductases
EC 1.17.4.4
Losartan
JMS50MPO89
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
109168Informations de copyright
Copyright © 2020. Published by Elsevier B.V.