The diversity and clinical implications of genetic variants influencing clopidogrel bioactivation and response in the Emirati population.
ABCB1
CYP2C19
Clopidogrel
Emirati population
Genetic variants
P2Y12R
PON1
Pharmacogenomics
Journal
Human genomics
ISSN: 1479-7364
Titre abrégé: Hum Genomics
Pays: England
ID NLM: 101202210
Informations de publication
Date de publication:
03 Jan 2024
03 Jan 2024
Historique:
received:
31
10
2023
accepted:
19
12
2023
medline:
4
1
2024
pubmed:
4
1
2024
entrez:
4
1
2024
Statut:
epublish
Résumé
Clopidogrel is a widely prescribed prodrug that requires activation via specific pharmacogenes to exert its anti-platelet function. Genetic variations in the genes encoding its transporter, metabolizing enzymes, and target receptor lead to variability in its activation and platelet inhibition and, consequently, its efficacy. This variability increases the risk of secondary cardiovascular events, and therefore, some variations have been utilized as genetic biomarkers when prescribing clopidogrel. Our study examined clopidogrel-related genes (CYP2C19, ABCB1, PON1, and P2Y12R) in a cohort of 298 healthy Emiratis individuals. The study used whole exome sequencing (WES) data to comprehensively analyze pertinent variations of these genes, including their minor allele frequencies, haplotype distribution, and their resulting phenotypes. Our data shows that approximately 37% (n = 119) of the cohort are likely to benefit from the use of alternative anti-platelet drugs due to their classification as intermediate or poor CYP2C19 metabolizers. Additionally, more than 50% of the studied cohort exhibited variants in ABCB1, PON1, and P2YR12 genes, potentially influencing clopidogrel's transport, enzymatic clearance, and receptor performance. Recognizing these alleles and genotype frequencies may explain the clinical differences in medication response across different ethnicities and predict adverse events. Our findings underscore the need to consider genetic variations in prescribing clopidogrel, with potential implications for implementing personalized anti-platelet therapy among Emiratis based on their genetic profiles.
Sections du résumé
BACKGROUND
BACKGROUND
Clopidogrel is a widely prescribed prodrug that requires activation via specific pharmacogenes to exert its anti-platelet function. Genetic variations in the genes encoding its transporter, metabolizing enzymes, and target receptor lead to variability in its activation and platelet inhibition and, consequently, its efficacy. This variability increases the risk of secondary cardiovascular events, and therefore, some variations have been utilized as genetic biomarkers when prescribing clopidogrel.
METHODS
METHODS
Our study examined clopidogrel-related genes (CYP2C19, ABCB1, PON1, and P2Y12R) in a cohort of 298 healthy Emiratis individuals. The study used whole exome sequencing (WES) data to comprehensively analyze pertinent variations of these genes, including their minor allele frequencies, haplotype distribution, and their resulting phenotypes.
RESULTS
RESULTS
Our data shows that approximately 37% (n = 119) of the cohort are likely to benefit from the use of alternative anti-platelet drugs due to their classification as intermediate or poor CYP2C19 metabolizers. Additionally, more than 50% of the studied cohort exhibited variants in ABCB1, PON1, and P2YR12 genes, potentially influencing clopidogrel's transport, enzymatic clearance, and receptor performance.
CONCLUSIONS
CONCLUSIONS
Recognizing these alleles and genotype frequencies may explain the clinical differences in medication response across different ethnicities and predict adverse events. Our findings underscore the need to consider genetic variations in prescribing clopidogrel, with potential implications for implementing personalized anti-platelet therapy among Emiratis based on their genetic profiles.
Identifiants
pubmed: 38173046
doi: 10.1186/s40246-023-00568-3
pii: 10.1186/s40246-023-00568-3
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2Subventions
Organisme : Ministry of Education, United Arab Emirates
ID : 1570604941 (UAEU code 21M139)
Organisme : Ministry of Education, United Arab Emirates
ID : 1570604941 (UAEU code 21M139)
Organisme : ASPIRE, the technology program management pillar of Abu Dhabi's Advanced Technology Research Council (ATRC), via the ASPIRE Precision Medicine Research Institute.
ID : VRI-20-10
Organisme : ASPIRE, the technology program management pillar of Abu Dhabi's Advanced Technology Research Council (ATRC), via the ASPIRE Precision Medicine Research Institute.
ID : VRI-20-10
Informations de copyright
© 2024. The Author(s).
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