| Autor: |
Verma, S.S. Bergmeijer, T.O. Gong, L. Reny, J.-L. Lewis, J.P. Mitchell, B.D. Alexopoulos, D. Aradi, D. Altman, R.B. Bliden, K. Bradford, Y. Campo, G. Chang, K. Cleator, J.H. Déry, J.-P. Dridi, N.P. Fernandez-Cadenas, I. Fontana, P. Gawaz, M. Geisler, T. Gensini, G.F. Giusti, B. Gurbel, P.A. Hochholzer, W. Holmvang, L. Kim, E.-Y. Kim, H.-S. Marcucci, R. Montaner, J. Backman, J.D. Pakyz, R.E. Roden, D.M. Schaeffeler, E. Schwab, M. Shin, J.G. Siller-Matula, J.M. ten Berg, J.M. Trenk, D. Valgimigli, M. Wallace, J. Wen, M.-S. Kubo, M. Lee, M.T.M. Whaley, R. Winter, S. Klein, T.E. Shuldiner, A.R. Ritchie, M.D. for the ICPC Investigators |
| Jazyk: |
angličtina |
| Rok vydání: |
2020 |
| Předmět: |
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| Popis: |
Antiplatelet response to clopidogrel shows wide variation, and poor response is correlated with adverse clinical outcomes. CYP2C19 loss-of-function alleles play an important role in this response, but account for only a small proportion of variability in response to clopidogrel. An aim of the International Clopidogrel Pharmacogenomics Consortium (ICPC) is to identify other genetic determinants of clopidogrel pharmacodynamics and clinical response. A genomewide association study (GWAS) was performed using DNA from 2,750 European ancestry individuals, using adenosine diphosphate-induced platelet reactivity and major cardiovascular and cerebrovascular events as outcome parameters. GWAS for platelet reactivity revealed a strong signal for CYP2C19*2 (P value = 1.67e−33). After correction for CYP2C19*2 no other single-nucleotide polymorphism reached genomewide significance. GWAS for a combined clinical end point of cardiovascular death, myocardial infarction, or stroke (5.0% event rate), or a combined end point of cardiovascular death or myocardial infarction (4.7% event rate) showed no significant results, although in coronary artery disease, percutaneous coronary intervention, and acute coronary syndrome subgroups, mutations in SCOS5P1, CDC42BPA, and CTRAC1 showed genomewide significance (lowest P values: 1.07e−09, 4.53e−08, and 2.60e−10, respectively). CYP2C19*2 is the strongest genetic determinant of on-clopidogrel platelet reactivity. We identified three novel associations in clinical outcome subgroups, suggestive for each of these outcomes. © 2020 The Authors. Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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