Influence of cytochrome 2C19 allelic variants on on-treatment platelet reactivity evaluated by five different platelet function tests |
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Authors: | Gremmel Thomas Kopp Christoph W Moertl Deddo Seidinger Daniela Koppensteiner Renate Panzer Simon Mannhalter Christine Steiner Sabine |
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Institution: | a Division of Angiology, Department of Internal Medicine II, Medical University of Vienna, Vienna, Austriab Division of Cardiology, Department of Internal Medicine II, Medical University of Vienna, Vienna, Austriac Clinical Department of Blood Group Serology and Transfusion Medicine, Division of Blood Group Serology, Medical University of Vienna, Vienna, Austriad Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria |
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Abstract: | BackgroundThe antiplatelet effect of clopidogrel has been linked to cytochrome P450 2C19 (CYP2C19) carrier status. The presence of loss of function and gain of function variants were found to have a gene-dose effect on clopidogrel metabolism. However, genotyping is only one aspect of predicting response to clopidogrel and several platelet function tests are available to measure platelet response.Patients and methodsWe studied the influence of CYP2C19 allelic variants on on-treatment platelet reactivity as assessed by light transmission aggregometry (LTA), the VerifyNow P2Y12 assay, the VASP assay, multiple electrode aggregometry (MEA), and the Impact-R in 288 patients after stenting for cardiovascular disease. Allelic variants of CYP2C19 were determined with the Infiniti® CYP450 2C19 + assay and categorized into four metabolizer states (ultrarapid, extensive, intermediate, poor).ResultsPlatelet reactivity increased linearly from ultrarapid to poor metabolizers using the VerifyNow P2Y12 assay (P = 0.04), the VASP assay (P = 0.02) and the Impact-R (P = 0.04). The proportion of patients with high on-treatment residual platelet reactivity (HRPR) identified by LTA, the VerifyNow P2Y12 assay and the VASP assay increased when the metabolizer status decreased, while no such relationship could be identified for results of MEA and Impact-R. The presence of loss of function variants (*2/*2, *2-8*/wt, *2/*17) was an independent predictor of HRPR in LTA and the VASP assay while it did not reach statistical significance in the VerifyNow P2Y12 assay, MEA, and the Impact-R.ConclusionDepending on the type of platelet function test differences in the association of on-treatment platelet reactivity with CYP2C19 carrier status are observed. |
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Keywords: | CYP cytochrome P450 ADP adenosine diphosphate HRPR high on-treatment residual ADP-inducible platelet reactivity LOF loss-of-function LTA light transmission aggregometry VASP vasodilator-stimulated phosphoprotein PRI platelet reactivity index PRU P2Y12 Reaction Units MEA multiple electrode aggregometry AU aggregation units SC surface coverage |
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