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- Title
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.
- 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.; de Boer, Anthonius; Klungel, Olaf H.; ten Berg, Jurriën M.; Deneer, Vera H. M.
- Abstract
This study aims to determine whether genetic variants that influence CYP3A4 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 CYP3A4*22 and PPAR-α (G209A and A208G) SNPs were genotyped and the VerifyNow P2Y12 platelet reactivity test was performed. Minor allele frequencies were 0.4% for CYP3A4*22/*22, 6.8% for PPAR-α G209A AA, and 7.0% for PPAR-α A208G GG. CYP3A4*22 was not associated with platelet reactivity. The PPAR-α genetic variants were significantly associated with platelet reactivity (G209A AA: −24.6 PRU [−44.7, −4.6], p = 0.016; A208G GG: −24.6 PRU [−44.3, −4.8], p = 0.015). Validation of these PPAR-α 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 (p = 0.04 for PPAR-a G209A and p = 0.03 for A208G), with no difference in statin/fibrate non-users. In conclusion, PPAR-α 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.
- Subjects
PERCUTANEOUS coronary intervention; ANTILIPEMIC agents; BLOOD platelets; CLOPIDOGREL; GENE frequency
- Publication
Genes, 2020, Vol 11, Issue 9, p1068
- ISSN
2073-4425
- Publication type
Article
- DOI
10.3390/genes11091068