Kirac D, Erdem A, Avcilar T, Yesilcimen K, Guney A I, Emre A, Yazici S, Terzi S, Kaspar E C, Cetin S E, Isbir T
Yeditepe University Faculty of Medicine, Department of Medical Biology Istanbul Turkey
Dr. Siyami Ersek Thoracic and Cardiovascular Surgery Training and Research Hospital Department of Cardiology Istanbul Turkey.
Cell Mol Biol (Noisy-le-grand). 2016 Jan 19;62(1):51-5.
Stent thrombosis (ST) is considered as a multifactorial problem which is mostly occurs due to clopidogrel resistance. It may be due to some CYP450 enzyme deficiencies which play role in clopidogrel metabolism. Therefore the aim of this study is to detect the mutations in CYP2C19 and CYP2C9 genes which may cause ST, and to investigate the relation between other risk factors and ST. 50 individuals who have stent thrombosis and 50 individuals who haven't got any complication were enrolled as patient and control group respectively. *2,*3,4,5,17 mutations in CYP2C19 gene and 2 ve 3 mutations in CYP2C9 gene were investigated with RT-PCR. Clopidogrel and aspirin resistance were investigated with multiple electrode platelet aggregometry. Results were evaluated statistically. CYP2C192 mutation was found statistically higher in patients (% 18), whereas CYP2C1917 was found statistically higher in controls (% 36)(p<0.05). Additionally, it was found that patients who have clopidogrel and/or aspirin resistance also have CYP2C191/2 or CYPC192/2 genotype. These relations were also found statistically significant. (p=0,000005 for clopidogrel resistance and p=0,000059 for aspirin resistance). In conclusion, it was suggested that there is a relation between CYP2C192 mutations and ST due to clopidogrel resistance, and CYP2C1917 may have a protective role in this process. The use of novel and more potent drug or high clopidogrel maintenance dosing before stent implantation may be beneficial treatment options for antiplatelet therapy in CYP2C192 carriers.
支架内血栓形成（ST）被认为是一个多因素问题，主要是由于氯吡格雷抵抗所致。这可能是由于一些参与氯吡格雷代谢的细胞色素P450酶缺乏。因此，本研究的目的是检测可能导致ST的CYP2C19和CYP2C9基因中的突变，并研究其他危险因素与ST之间的关系。分别纳入50例发生支架内血栓形成的个体和50例未发生任何并发症的个体作为患者组和对照组。采用逆转录聚合酶链反应（RT-PCR）检测CYP2C19基因的2、3、4、5、17突变以及CYP2C9基因的2和3突变。采用多电极血小板聚集测定法检测氯吡格雷和阿司匹林抵抗情况。对结果进行统计学评估。结果发现，患者中CYP2C192突变在统计学上更高（18%），而对照组中CYP2C1917在统计学上更高（36%）（p<0.05）。此外，还发现存在氯吡格雷和/或阿司匹林抵抗的患者也具有CYP2C191/2或CYPC192/2基因型。这些关系在统计学上也具有显著性。（氯吡格雷抵抗p=0.000005，阿司匹林抵抗p=0.000059）。总之，提示CYP2C192突变与因氯吡格雷抵抗导致的ST之间存在关联，而CYP2C1917在此过程中可能具有保护作用。对于CYP2C192携带者，在支架植入前使用新型且更有效的药物或高剂量维持氯吡格雷治疗可能是抗血小板治疗的有益选择。
