Effect of CYP3A4 22 and PPAR-α Genetic Variants on Platelet Reactivity in Patients Treated with Clopidogrel and Lipid-Lowering Drugs Undergoing Elective Percutaneous Coronary Intervention

This study aims to determine whether genetic variants that influence expression are associated with platelet reactivity in clopidogrel-treated patients undergoing elective percutaneous coronary intervention (PCI), and to evaluate the influence of statin/fibrate co-medication on these associations. A...

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Bibliographic Details
Published in:Genes 2020-09, Vol.11 (9)
Main Authors: Bergmeijer, Thomas O, Yasmina, Alfi, Vos, Gerrit J A, Janssen, Paul W A, Hackeng, Christian M, Kelder, Johannes C, Verma, Shefali S, Ritchie, Marylyn D, Gong, Li, Klein, Teri E, Icpc Investigators, de Boer, Anthonius, Klungel, Olaf H, Ten Berg, Jurriën M, Deneer, Vera H M
Format: Article
Language:English
Subjects:
Aged
Anticholesteremic Agents - therapeutic use
Blood Platelets - drug effects
Clopidogrel - therapeutic use
Cohort Studies
Coronary Artery Disease - drug therapy
Coronary Artery Disease - genetics
Coronary Artery Disease - pathology
Cytochrome P-450 CYP3A - genetics
Female
Humans
Male
Percutaneous Coronary Intervention - methods
Platelet Aggregation Inhibitors - therapeutic use
Polymorphism, Genetic
PPAR alpha - genetics
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Summary:This study aims to determine whether genetic variants that influence expression are associated with platelet reactivity in clopidogrel-treated patients undergoing elective percutaneous coronary intervention (PCI), and to evaluate the influence of statin/fibrate co-medication on these associations. A study cohort was used containing 1124 consecutive elective PCI patients in whom *22 and (G209A and A208G) SNPs were genotyped and the VerifyNow P2Y platelet reactivity test was performed. Minor allele frequencies were 0.4% for *22/*22, 6.8% for G209A AA, and 7.0% for A208G GG. *22 was not associated with platelet reactivity. The genetic variants were significantly associated with platelet reactivity (G209A AA: -24.6 PRU [-44.7, -4.6], = 0.016; A208G GG: -24.6 PRU [-44.3, -4.8], = 0.015). Validation of these results in two external cohorts, containing 716 and 882 patients, respectively, showed the same direction of effect, although not statistically significant. Subsequently, meta-analysis of all three cohorts showed statistical significance of both variants in statin/fibrate users ( = 0.04 for G209A and = 0.03 for A208G), with no difference in statin/fibrate non-users. In conclusion, G209A and A208G were associated with lower platelet reactivity in patients undergoing elective PCI who were treated with clopidogrel and statin/fibrate co-medication. Further research is necessary to confirm these findings.
ISSN:2073-4425