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Clopidogrel Pharmacogenetics in Iranian Patients Undergoing Percutaneous Coronary Intervention
Nejat Mahdieh1, Ahmad Rabbani2, Ata Firouzi2
1Medical Genetics Laboratory, Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Valiasr Street, Niyaesh Intersection, Tehran, 1995614331, Iran.
Insights
Genetic variations in CYP2C19, CYP3A5, CYP3A4, and ABCB1 genes do not individually predict clopidogrel treatment outcomes in Iranian patients undergoing PCI. Combined genetic factors, not single gene variants, influence drug response and cardiovascular events.
Area of Science:
- Pharmacogenetics
- Cardiovascular Medicine
- Genomics
Background:
- Clopidogrel is a crucial antiplatelet medication for patients with coronary syndromes and those undergoing percutaneous coronary intervention (PCI).
- Patient response to clopidogrel can vary due to genetic factors affecting drug metabolism and efficacy.
- Understanding these genetic influences is vital for optimizing treatment and reducing thrombotic events like heart attack and stroke.
Purpose of the Study:
- To investigate the association between common genetic variants in CYP2C19, CYP3A5, CYP3A4, and ABCB1 genes and cardiovascular outcomes in Iranian patients treated with clopidogrel after PCI.
- To determine if individual gene variants or combinations of variants impact treatment efficacy and patient safety.
Main Methods:
- A cohort of 388 Iranian patients undergoing PCI and treated with clopidogrel was studied over a 6-month follow-up period.
- Genotyping was performed for six single nucleotide polymorphisms (SNPs): CYP2C19*2, CYP2C19*3, CYP2C19*17, ABCB1 (c.3435C>T), CYP3A5 (c.6986A>G), and CYP3A4 (c.1026+12G>A).
- Cardiovascular events, including thrombosis, unstable angina, and non-STEMI, were recorded to assess treatment outcomes.
Main Results:
- None of the individually genotyped SNPs showed a significant association with cardiovascular events in patients treated with clopidogrel.
- The studied genetic variants were found to be in Hardy-Weinberg equilibrium.
- Eight patients experienced cardiovascular events during the follow-up period.
Conclusions:
- Individual genetic variants in CYP2C19, CYP3A5, CYP3A4, and ABCB1 are not sufficient predictors of clopidogrel treatment outcomes after PCI.
- Combinations of genetic alleles appear to play a significant role in pharmacokinetic variability and overall treatment response.
- These findings underscore the complexity of pharmacogenetics and highlight the importance of personalized medicine approaches for accurate risk assessment and tailored treatment strategies.
Abstract:
Clopidogrel is used in patients with coronary syndromes and at risk of thrombotic events or receiving percutaneous coronary intervention (PCI) for reducing heart attack and stroke. Here we present genotype and phenotype study of Iranian patients undergoing PCI treated with clopidogrel during a 6-month period of follow-up; common variants of CYP2C19, CYP3A5, CYP3A4, and ABCB1 genes were determined as well as the patients' cardiovascular outcomes to find out the effect of these variants individually and in combination. 388 individuals receiving PCI were enrolled in this study. Different pretreatment doses of clopidogrel were prescribed under the interventional cardiologists' guidance. The patients were followed for a duration of 1 month, and 6 months. Six SNPs were selected for genotyping including CYP2C19*2 (c.681G > A), CYP2C19*3 (c.636G > A), CYP2C19*17 allele (c.-806C > T), ABCB1 (c.3435C > T), CYP3A5 (c.6986A > G), and CYP3A4 (c.1026 + 12G > A). The mean loading dose was 600 mg/day in 267 (68.8%) individuals, 300 mg/day in 121 (31.2%). 8 patients had cardiovascular events such as thrombosis, unstable angina, and non-STEMI. The studied alleles and genotypes were in Hardy-Weinberg equilibrium. None of the SNPs individually were significantly associated with outcome events. Our results indicate that combinations of different alleles of genes are involved in pharmacokinetic variability and joint factors are important; this means that genotyping and analysis of an individual variant may not be as straightforward in risk assessment and pharmacogenetics. This highlights the importance of personalized medicine in risk assessment and treatment.
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