Cytochrome P450 2C19 enzyme, Cytochrome P450 2C9 enzyme, and Cytochrome P450 2D6 enzyme allelic variants and its possible effect on drug metabolism

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

The objective of the present study was to assess the allelic variations of Cytochrome P450 (CYP) enzymes Cytochrome P450 2C19 (CYP2C19), Cytochrome P450 2C9 (CYP2C9), and Cytochrome P450 2D6 (CYP2D6) as they play a major role in drug metabolism. The interindividual genetic variabilities of these enzymes can account for different responsiveness as well as concentration fluctuations for a particular drug.

During the period of 2017 to 2018 a total of 54 patients have received pharmacogenetic testing at the Department of Genetics and Molecular Medicine at Kaunas Clinics. According to the genotype-metabolic phenotypes of CYP2C19, CYP2D6, CYP2C9 enzymes patients were classified according to the guidelines by Clinical Pharmacogenetics Implementation Consortium (CPIC): normal metabolizers (NMs), intermediate metabolizers (IMs), rapid metabolizers (RMs), ultrarapid metabolizers (UMs), and poor metabolizers (PMs).

CYP2C19 enzyme allelic distribution: 18 patients (33.33%) with ∗1/∗1 genotype were NMs; 14 patients (25.93%) with ∗1/∗2; ∗2/∗17 genotypes were classified as IMs; 15 patients (27.78%) possessed ∗1/∗17 genotype and were RMs; 4 patients (7.4%) had ∗17/∗17 genotype with increased enzyme activity compared with RMs, were classified as UMs; 3 patients (5.56%) had ∗2/∗2 genotype and were marked as PMs. CYP2D6 enzyme allelic distribution: 26 patients (48.148%) contained ∗1/∗1,∗2/∗2,∗1/∗2,∗1/∗41,∗2/∗41 genotypes with normal enzymatic function so were accounted as NMs; 21 patients (38.89%) with ∗1/∗5, ∗2/∗4, ∗10/∗41, ∗1/∗4, ∗1/∗3, ∗2/∗5, ∗2/∗4, ∗2/∗6 genotypes were accounted as IMs; 2 patients (3.7%) possessed ∗2XN genotype and were accounted as UMs and 5 patients (9.26%) possessed ∗4/∗5,∗4/∗10,∗4/∗9,∗4/∗41 genotypes and had non-functional enzymatic activity so were accounted as PMs; CYP2C9 enzyme allelic distribution: 44 patients (81.48%) with∗1/∗1 genotype were NMs; 10 patients (18.52%) with ∗1/∗2;∗1/∗3 genotypes were IMs.

The results of our study indicate that deviations from the normal enzymatic activity is common amongst Lithuanian people and combinatory genotyping of CYP2D6, CYP2C9, and CYP2C19 has to be promoted as an advanced method because of most commonly prescribed medicines like analgesics, antihypertensive, antidepressants are metabolized by multiple pathways involving enzymes in the CYP450 family.

Related collections

Most cited references 39

Record: found
Abstract: found
Article: not found

Clinical Pharmacogenetics Implementation Consortium guidelines for CYP2C19 genotype and clopidogrel therapy: 2013 update.

S A Scott, K Sangkuhl, C. M. Stein … (2013)

Cytochrome P450 (CYP)2C19 catalyzes the bioactivation of the antiplatelet prodrug clopidogrel, and CYP2C19 loss-of-function alleles impair formation of active metabolites, resulting in reduced platelet inhibition. In addition, CYP2C19 loss-of-function alleles confer increased risks for serious adverse cardiovascular (CV) events among clopidogrel-treated patients with acute coronary syndromes (ACSs) undergoing percutaneous coronary intervention (PCI). Guideline updates include emphasis on appropriate indication for CYP2C19 genotype-directed antiplatelet therapy, refined recommendations for specific CYP2C19 alleles, and additional evidence from an expanded literature review (updates at http://www.pharmgkb.org).

0 comments Cited 281 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Influence of cytochrome P450 polymorphisms on drug therapies: pharmacogenetic, pharmacoepigenetic and clinical aspects.

Magnus Ingelman-Sundberg, Sarah C Sim, Alvin Gomez … (2007)

The polymorphic nature of the cytochrome P450 (CYP) genes affects individual drug response and adverse reactions to a great extent. This variation includes copy number variants (CNV), missense mutations, insertions and deletions, and mutations affecting gene expression and activity of mainly CYP2A6, CYP2B6, CYP2C9, CYP2C19 and CYP2D6, which have been extensively studied and well characterized. CYP1A2 and CYP3A4 expression varies significantly, and the cause has been suggested to be mainly of genetic origin but the exact molecular basis remains unknown. We present a review of the major polymorphic CYP alleles and conclude that this variability is of greatest importance for treatment with several antidepressants, antipsychotics, antiulcer drugs, anti-HIV drugs, anticoagulants, antidiabetics and the anticancer drug tamoxifen. We also present tables illustrating the relative importance of specific common CYP alleles for the extent of enzyme functionality. The field of pharmacoepigenetics has just opened, and we present recent examples wherein gene methylation influences the expression of CYP. In addition microRNA (miRNA) regulation of P450 has been described. Furthermore, this review updates the field with respect to regulatory initiatives and experience of predictive pharmacogenetic investigations in the clinics. It is concluded that the pharmacogenetic knowledge regarding CYP polymorphism now developed to a stage where it can be implemented in drug development and in clinical routine for specific drug treatments, thereby improving the drug response and reducing costs for drug treatment.

0 comments Cited 228 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: found

Is Open Access

Worldwide Distribution of Cytochrome P450 Alleles: A Meta‐analysis of Population‐scale Sequencing Projects

Y Zhou, M Ingelman-Sundberg, VM Lauschke (2017)

Genetic polymorphisms in cytochrome P450 (CYP) genes can result in altered metabolic activity toward a plethora of clinically important medications. Thus, single nucleotide variants and copy number variations in CYP genes are major determinants of drug pharmacokinetics and toxicity and constitute pharmacogenetic biomarkers for drug dosing, efficacy, and safety. Strikingly, the distribution of CYP alleles differs considerably between populations with important implications for personalized drug therapy and healthcare programs. To provide a global distribution map of CYP alleles with clinical importance, we integrated whole‐genome and exome sequencing data from 56,945 unrelated individuals of five major human populations. By combining this dataset with population‐specific linkage information, we derive the frequencies of 176 CYP haplotypes, providing an extensive resource for major genetic determinants of drug metabolism. Furthermore, we aggregated this dataset into spectra of predicted functional variability in the respective populations and discuss the implications for population‐adjusted pharmacological treatment strategies.

0 comments Cited 199 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Journal

Journal ID (nlm-ta): Medicine (Baltimore)

Journal ID (iso-abbrev): Medicine (Baltimore)

Journal ID (publisher-id): MEDI

Title: Medicine

Publisher: Lippincott Williams & Wilkins (Hagerstown, MD )

ISSN (Print): 0025-7974

ISSN (Electronic): 1536-5964

Publication date Collection: 19 March 2021

Publication date (Electronic): 19 March 2021

Volume: 100

Issue: 11

Electronic Location Identifier: e24545

Affiliations

[a ]Faculty of Pharmacy, Lithuanian University of Health Sciences

[b ]Department of Genetics and Molecular Medicine, Hospital of Lithuanian University of Health Sciences

[c ]Institute of Physiology and Pharmacology, Faculty of Medicine, Medical Academy, Lithuanian University of Health Sciences, Kaunas, Lithuania.

Author notes

[∗ ]Correspondence: Domas Naujokaitis, Faculty of Pharmacy, Lithuanian University of Health Sciences, Sukileliai av.13, LT-50166, Kaunas, Lithuania (e-mail: domas.naujokaitis@ 123456gmail.com ).

Author information

Domas Naujokaitis http://orcid.org/0000-0003-2125-0837

Article

Publisher ID: MD-D-19-06236 Accession ID: 24545

DOI: 10.1097/MD.0000000000024545

PMC ID: 7982200

PubMed ID: 33725937

SO-VID: ddf97426-a6ec-42b6-8295-1fc5e3ff410a

License:

This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/licenses/by/4.0

History

Date received : 7 August 2019

Date revision received : 17 November 2020

Date accepted : 7 January 2021

Custom metadata

OPEN-ACCESS TRUE

Keywords: allelic variations,cytochrome p450 2c19 enzyme,cytochrome p450 2c9 enzyme,cytochrome p450 2d6 enzyme,drug concentrations,drug metabolism

Data availability:

Keywords: allelic variations, cytochrome p450 2c19 enzyme, cytochrome p450 2c9 enzyme, cytochrome p450 2d6 enzyme, drug concentrations, drug metabolism

Cytochrome P450 2C19 enzyme, Cytochrome P450 2C9 enzyme, and Cytochrome P450 2D6 enzyme allelic variants and its possible effect on drug metabolism : A retrospective study

Read this article at

Abstract

Related collections

Network Medicine

Most cited references 39

Clinical Pharmacogenetics Implementation Consortium guidelines for CYP2C19 genotype and clopidogrel therapy: 2013 update.

Influence of cytochrome P450 polymorphisms on drug therapies: pharmacogenetic, pharmacoepigenetic and clinical aspects.

Worldwide Distribution of Cytochrome P450 Alleles: A Meta‐analysis of Population‐scale Sequencing Projects

Author and article information

Journal

Affiliations

Author notes

Author information

Article

History

Categories

Custom metadata

Comments

Comment on this article

Similar content 223

Cited by 5

Most referenced authors 377