CYP2C192 and other genetic variants affecting platelet response to clopidogrel in patients undergoing percutaneous coronary intervention

• Published in: Thrombosis research 2012-04, Vol.129 (4), p.441-446
• Main Authors: Kassimis, George, Davlouros, Periklis, Xanthopoulou, Ioanna, Stavrou, Eleana F, Athanassiadou, Aglaia, Alexopoulos, Dimitrios
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Clopidogrel; Comorbidity; Coronary Artery Disease - blood; Coronary Artery Disease - epidemiology; Coronary Artery Disease - surgery; Coronary heart disease; CYP2B65; CYP2C19; Cytokines - genetics; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Female; Genetic Predisposition to Disease - epidemiology; Genetic Predisposition to Disease - genetics; Greece - epidemiology; Heart; Hematology, Oncology and Palliative Medicine; Humans; Male; Medical sciences; P2RY12; Percutaneous coronary intervention; Platelet Activation - drug effects; Platelet Activation - genetics; Platelet Aggregation Inhibitors - therapeutic use; Platelet reactivity; Prevalence; Stents - statistics & numerical data; Thrombosis - epidemiology; Thrombosis - genetics; Thrombosis - prevention & control; Ticlopidine - analogs & derivatives; Ticlopidine - therapeutic use; Treatment Outcome
• ISSN: 0049-3848; 1879-2472
• DOI: 10.1016/j.thromres.2011.07.022

Abstract Introduction Information regarding any possible additional effect of genetic variants other than CYP2C19*2 on platelet reactivity in patients undergoing percutaneous coronary intervention (PCI), while on dual antiplatelet therapy, is sparse. Materials and Methods Genotyping for CYP2C19*2 , CYP2C19*17 , CYP2C9*3 , CYP2B6*5 , ABCB1 and P2RY12 (c.-217 + 2739 T > C) variants was performed in 146 consecutive PCI patients receiving clopidogrel. Platelet reactivity was assessed by the Verify Now P2Y12 point-of-care assay and high on-treatment platelet reactivity (HTPR) was defined as a Platelet Reactivity Unit (PRU) ≥ 235. Results We identified 65(44.5%) patients with HTPR and 38(26%) carriers of at least one CYP2C19*2 allele, which had higher platelet reactivity compared to non-carriers [least square (LS) mean difference 44.5, 95%CI 15.8-77.3, p = 0.003]. In the entire study population, the presence of at least one CYP2C19*2 or P2RY12 allelic variant was independently associated with HTPR (OR = 3.02, 95%CI 1.16-7.86, p = 0.023 and OR = 3.11, 95%CI 1.03-9.39, p = 0.05 respectively). In CYP2C19*2 non-carriers, carriers of at least one CYP2B6*5 allelic variant had higher platelet reactivity compared to the remainders (LS mean difference 35.6, 95%CI 3.7-67.6, p = 0.03) and the presence of at least one CYP2B6*5 or P2RY12 allelic variant was independently associated with HTPR (OR = 3.26, 95%CI 1.08-9.86, p = 0.04 and OR = 4.27, 95%CI 1.11-16.4, p = 0.04 respectively). Conclusions Apart from the CYP2C19*2 , other genetic variants involved in clopidogrel metabolism and action like CYP2B6*5 and P2RY12 seem to have an important association with HTPR.