Decreased platelet responsiveness to clopidogrel correlates with CYP2C19 and PON1 polymorphisms in atherosclerotic patients
Clopidogrel and aspirin are the most commonly used medications worldwide for dual antiplatelet therapy after percutaneous coronary intervention. However, clopidogrel hyporesponsiveness related to gene polymorphisms is a concern. Populations with higher degrees of genetic admixture may have increased...
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| Format: | Article |
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Associação Brasileira de Divulgação Científica
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| Series: | Brazilian Journal of Medical and Biological Research |
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| Online Access: | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2017000100702&lng=en&tlng=en |
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| author | J.F.M. Marchini M.R. Pinto G.C. Novaes A.V. Badran R.B. Pavão G.L. Figueiredo I.M. Lago M.O. Lima-Filho D.C. Lemos M. Tonani C.M. Antloga L. Oliveira J.C. Lorenzi J.A. Marin-Neto |
| author_facet | J.F.M. Marchini M.R. Pinto G.C. Novaes A.V. Badran R.B. Pavão G.L. Figueiredo I.M. Lago M.O. Lima-Filho D.C. Lemos M. Tonani C.M. Antloga L. Oliveira J.C. Lorenzi J.A. Marin-Neto |
| author_sort | J.F.M. Marchini |
| collection | DOAJ |
| description | Clopidogrel and aspirin are the most commonly used medications worldwide for dual antiplatelet therapy after percutaneous coronary intervention. However, clopidogrel hyporesponsiveness related to gene polymorphisms is a concern. Populations with higher degrees of genetic admixture may have increased prevalence of clopidogrel hyporesponsiveness. To assess this, we genotyped CYP2C19, ABCB1, and PON1 in 187 patients who underwent percutaneous coronary intervention. Race was self-defined by patients. We also performed light transmission aggregometry with adenosine diphosphate (ADP) and arachidonic acid during dual antiplatelet therapy. We found a significant difference for presence of the CYP2C19*2 polymorphism between white and non-white patients. Although 7% of patients had platelet resistance to clopidogrel, this did not correlate with any of the tested genetic polymorphisms. We did not find platelet resistance to aspirin in this cohort. Multivariate analysis showed that patients with PON1 and CYP2C19 polymorphisms had higher light transmission after ADP aggregometry than patients with native alleles. There was no preponderance of any race in patients with higher light transmission aggregometry. In brief, PON1 and CYP2C19 polymorphisms were associated with lower clopidogrel responsiveness in this sample. Despite differences in CYP2C19 polymorphisms across white and non-white patients, genetic admixture by itself was not able to identify clopidogrel hyporesponsiveness. |
| first_indexed | 2024-12-14T01:16:07Z |
| format | Article |
| id | doaj.art-3d124b31a20e47f180ae25207c958305 |
| institution | Directory Open Access Journal |
| issn | 1414-431X |
| language | English |
| last_indexed | 2024-12-14T01:16:07Z |
| publisher | Associação Brasileira de Divulgação Científica |
| record_format | Article |
| series | Brazilian Journal of Medical and Biological Research |
| spelling | doaj.art-3d124b31a20e47f180ae25207c9583052022-12-21T23:22:34ZengAssociação Brasileira de Divulgação CientíficaBrazilian Journal of Medical and Biological Research1414-431X50110.1590/1414-431x20165660S0100-879X2017000100702Decreased platelet responsiveness to clopidogrel correlates with CYP2C19 and PON1 polymorphisms in atherosclerotic patientsJ.F.M. MarchiniM.R. PintoG.C. NovaesA.V. BadranR.B. PavãoG.L. FigueiredoI.M. LagoM.O. Lima-FilhoD.C. LemosM. TonaniC.M. AntlogaL. OliveiraJ.C. LorenziJ.A. Marin-NetoClopidogrel and aspirin are the most commonly used medications worldwide for dual antiplatelet therapy after percutaneous coronary intervention. However, clopidogrel hyporesponsiveness related to gene polymorphisms is a concern. Populations with higher degrees of genetic admixture may have increased prevalence of clopidogrel hyporesponsiveness. To assess this, we genotyped CYP2C19, ABCB1, and PON1 in 187 patients who underwent percutaneous coronary intervention. Race was self-defined by patients. We also performed light transmission aggregometry with adenosine diphosphate (ADP) and arachidonic acid during dual antiplatelet therapy. We found a significant difference for presence of the CYP2C19*2 polymorphism between white and non-white patients. Although 7% of patients had platelet resistance to clopidogrel, this did not correlate with any of the tested genetic polymorphisms. We did not find platelet resistance to aspirin in this cohort. Multivariate analysis showed that patients with PON1 and CYP2C19 polymorphisms had higher light transmission after ADP aggregometry than patients with native alleles. There was no preponderance of any race in patients with higher light transmission aggregometry. In brief, PON1 and CYP2C19 polymorphisms were associated with lower clopidogrel responsiveness in this sample. Despite differences in CYP2C19 polymorphisms across white and non-white patients, genetic admixture by itself was not able to identify clopidogrel hyporesponsiveness.http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2017000100702&lng=en&tlng=enPlatelet function testsSingle nucleotide polymorphismPercutaneous coronary interventionAspirinClopidogrel |
| spellingShingle | J.F.M. Marchini M.R. Pinto G.C. Novaes A.V. Badran R.B. Pavão G.L. Figueiredo I.M. Lago M.O. Lima-Filho D.C. Lemos M. Tonani C.M. Antloga L. Oliveira J.C. Lorenzi J.A. Marin-Neto Decreased platelet responsiveness to clopidogrel correlates with CYP2C19 and PON1 polymorphisms in atherosclerotic patients Brazilian Journal of Medical and Biological Research Platelet function tests Single nucleotide polymorphism Percutaneous coronary intervention Aspirin Clopidogrel |
| title | Decreased platelet responsiveness to clopidogrel correlates with CYP2C19 and PON1 polymorphisms in atherosclerotic patients |
| title_full | Decreased platelet responsiveness to clopidogrel correlates with CYP2C19 and PON1 polymorphisms in atherosclerotic patients |
| title_fullStr | Decreased platelet responsiveness to clopidogrel correlates with CYP2C19 and PON1 polymorphisms in atherosclerotic patients |
| title_full_unstemmed | Decreased platelet responsiveness to clopidogrel correlates with CYP2C19 and PON1 polymorphisms in atherosclerotic patients |
| title_short | Decreased platelet responsiveness to clopidogrel correlates with CYP2C19 and PON1 polymorphisms in atherosclerotic patients |
| title_sort | decreased platelet responsiveness to clopidogrel correlates with cyp2c19 and pon1 polymorphisms in atherosclerotic patients |
| topic | Platelet function tests Single nucleotide polymorphism Percutaneous coronary intervention Aspirin Clopidogrel |
| url | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2017000100702&lng=en&tlng=en |
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