ArticleDrug metabolism and drug interactions2013
Regulatory polymorphisms in CYP2C19 affecting hepatic expression.
Article in Drug metabolism and drug interactions, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 34 citations in OpenAlex.
- Exploring the roles of cytochrome P450 enzymes and their inhibitors in cancers and non-neoplastic human diseases.Archives of pharmacal research · 2025Review
- Comprehensive Molecular Evaluation of Transcription Factor 7-like 2, Long Noncoding RNA (ANRIL), and CYP2C19*17 Gene Variants and Their Association with Predisposition and Progression in Stroke Patients.Cellular and molecular neurobiology · 2025Article
- CYP2C19 gene polymorphism in Ningxia.Pharmacological reports : PR · 2023Article
- Omeprazole Treatment Failure in Gastroesophageal Reflux Disease and Genetic Variation at theFrontiers in genetics · 2022Article
- Sources of Interindividual Variability.Methods in molecular biology (Clifton, N.J.) · 2021Article
- Article
- Genomic resources for dissecting the role of non-protein coding variation in gene-environment interactions.Toxicology · 2020Review
- Impact of cytochrome P450 variation on meperidineXenobiotica; the fate of foreign compounds in biological systems · 2020Article
- Development and validation of T-ARMS-PCR to detect CYP2C19*17 allele.Journal of clinical laboratory analysis · 2020Article
- Influence of CYP2C19 Metabolizer Status on Escitalopram/Citalopram Tolerability and Response in Youth With Anxiety and Depressive Disorders.Frontiers in pharmacology · 2019Article
- Cytochrome P450: Polymorphisms and Roles in Cancer, Diabetes and AtherosclerosisAsian Pacific journal of cancer prevention : APJCP · 2018Review
- Pharmacogenomic Impact of CYP2C19 Variation on Clopidogrel Therapy in Precision Cardiovascular Medicine.Journal of personalized medicine · 2018Review
- Interindividual variability of CYP2C19-catalyzed drug metabolism due to differences in gene diplotypes and cytochrome P450 oxidoreductase content.The pharmacogenomics journal · 2016Article
- CYP2C9, CYP2C19, ABCB1 genetic polymorphisms and phenytoin plasma concentrations in Mexican-Mestizo patients with epilepsy.The pharmacogenomics journal · 2016Article
- The effect of polymorphic metabolism enzymes on serum phenytoin level.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2015Article
- Genome-wide discovery of drug-dependent human liver regulatory elements.PLoS genetics · 2014Article
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundCytochrome P450 2C19 is responsible for the metabolism of many drugs, including the activation of clopidogrel. The allele CYP2C19*17 is associated with ultra-rapid metabolizer phenotypes by increasing gene transcription. This study tests to what extent CYP2C19*17 enhances CYP2C19 expression in human liver and whether additional regulatory variants contribute to variation in CYP2C19 expression.
methodsCYP2C19 mRNA was measured with quantitative real-time PCR (qRT-PCR), enzyme activity as metabolic velocity with S-mephenytoin as the substrate and allelic mRNA expression ratio with SNaPshot in human livers. CYP2C19 transcribed exons and a 4kb promoter region were sequenced using IonTorrent PGM or Sanger sequencing and screened for polymorphisms associated with total hepatic CYP2C19 mRNA, enzyme activity and allelic mRNA ratios.
resultsLivers heterozygote and homozygous for CYP2C19*17 had mRNA levels 1.8-fold (p=0.028) and 2.9-fold (p=0.006), respectively, above homozygous reference allele livers. CYP2C19*17 heterozygotes were also associated with increased allelic mRNA expression (allelic ratio ~1.8-fold, SD±0.6, p<0.005), whereas CYP2C19 enzyme activity was elevated 2.3-fold, with borderline significance (p=0.06) in CYP2C19*17 carriers. One liver sample of African ancestry displayed a 2-fold allelic expression ratio, and another sample, a ~12-fold increase in metabolic velocity. Neither case was accounted for by *17, which indicates the presence of additional regulatory variants.
conclusionsOur findings confirm *17 as a regulatory polymorphism enhancing hepatic CYP2C19 expression 2-fold with potential to compensate for the loss of function allele CYP2C19*2. Additional regulatory factors may also enhance CYP2C19 expression in African American populations.
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