Interaction between platelet-derived microRNAs and CYP2C19*2 genotype on clopidogrel antiplatelet responsiveness in patients with ACS
| Autor: | Tong Yin, Jun Liu, Shaozhi Xi, Jia Liu, Li Peng, Caiyi Lu, Liuan Qin |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Oncology Blood Platelets Male medicine.medical_specialty Acute coronary syndrome Ticlopidine Genotype CYP2C19 030204 cardiovascular system & hematology 03 medical and health sciences 0302 clinical medicine Internal medicine microRNA medicine Humans Platelet In patient cardiovascular diseases Prospective Studies Acute Coronary Syndrome Genotyping Polymorphism Genetic business.industry Hematology Middle Aged medicine.disease Clopidogrel Cytochrome P-450 CYP2C19 MicroRNAs 030104 developmental biology Cardiology Female business Platelet Aggregation Inhibitors circulatory and respiratory physiology medicine.drug |
| Zdroj: | Thrombosis research. 157 |
| ISSN: | 1879-2472 |
| Popis: | Both platelet-derived microRNAs and the genotype of CYP2C19*2 were implicated for the variability of clopidogrel antiplatelet responsiveness. However, their interaction on the antiplatelet responsiveness of clopidogrel in patients with acute coronary syndrome (ACS) remains unknown.Consecutive clopidogrel-treated patients with ACS were recruited, with their antiplatelet responsiveness evaluated by the relative platelet inhibition (RI), as measured by light transmittance aggregometry (LTA) at baseline and 5days' after the maintenance treatment of clopidogrel. Extreme cases were selected according to the octiles of RI value. Expression of the microRNAs targeting the mRNAs of P2RY12 was analyzed in the platelet of the extreme cases. Genotyping of CYP2C19*2 was performed for each extreme case.Among the included 272 ACS patients, 21 cases were screened as the extremely high-responders with RI84%, and 18 as the extremely low-responders with RI10%. Bioinformatics tools predicted the candidate microRNAs of miR-223, miR-221, and miR-21 could bind directly to the mRNA of P2RY12. Compared with the extremely low-responders, the expression of miR-223, miR-221, and miR-21 was significantly higher in the extremely high-responders (miR-223: 7.18±2.95 vs. 0.99±0.64, p=0.022; miR-221: 3.60±2.54 vs. 1.14±0.81, p=0.004; miR-21: 4.36±3.33 vs. 2.31±1.69, p=0.01). ROC curve showed ideal discriminatory power of the platelet-derived miRNAs for the prediction of clopidogrel antiplatelet responsiveness (c-index=0.70 for miR-223; c-index=0.76 for miR-221; c-index=0.79 for miR-21). After stratified by the carrier status of CYP2C19*2, the association between platelet-derived miRNAs and clopidogrel antiplatelet responsiveness could be found only in CYP2C19*2 carriers, but not in non-carriers.Platelet-derived miRNAs (miR-223, miR-221 and miR-21) are independently associated with clopidogrel antiplatelet responsiveness in ACS patients. However, the association could be influenced by the interaction with CYP2C19*2 genotype. |
| Databáze: | OpenAIRE |
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