Nestorovska K A, Naumovska Z, Staninova Stojovska M, Sterjev Z, Dimovski A, Suturkova Lj
Faculty of Pharmacy, Ss. Cyril and Methodius University in Skopje, Skopje, RN Macedonia.
Balkan J Med Genet. 2024 Mar 12;26(2):35-40. doi: 10.2478/bjmg-2023-0023. eCollection 2023 Dec.
Clopidogrel, is a standard treatment in the prevention of major adverse cardiovascular events (MACE) in patients with coronary artery disease (CAD). Clopidogrel response is highly variable, mainly due to the presence of polymorphisms in the genes involved in drug metabolism. The aim of this study was to evaluate the association between the presence of the C3435T and 2 polymorphism and the clinical outcome in patients with CAD treated with clopidogrel. A total of 96 patients with CAD were included in the study. Genomic DNA from peripheral blood was extracted from all patients with standard phenol/chloroform protocol. The genotyping was performed by Real-Time PCR using TagMan assays. The frequency of the reduced-function allele, in both genes, was higher in patients with negative outcome (36.36% vs 21.15%). A negative clinical outcome and an increased risk for MACE was observed in patients with concomitant inheritance of the *1/*2 and CT genotype vs patients with other genotypes (22.73% vs 9.62%; OR 3.455; 95% CI= [0.936-12.743], p=0.05722. A trend towards higher risk of MACE was also noted in carriers of the and CC/CT genotype. Our results support the data on the association of the alone, or in combination with the C polymorphism with the increased risk of MACE. The results also indicate that the presence of C343T polymorphism might be potentially considered as independent predictor of MACE in patients on clopidogrel. However, these results are preliminary and should be confirmed on a larger number of patients.
氯吡格雷是预防冠心病（CAD）患者发生主要不良心血管事件（MACE）的标准治疗药物。氯吡格雷的反应存在高度变异性，主要是由于参与药物代谢的基因中存在多态性。本研究的目的是评估C3435T和2多态性的存在与接受氯吡格雷治疗的CAD患者临床结局之间的关联。共有96例CAD患者纳入本研究。采用标准酚/氯仿法从所有患者外周血中提取基因组DNA。使用TaqMan分析通过实时PCR进行基因分型。在预后不良的患者中，两个基因中功能降低等位基因的频率更高（36.36%对21.15%）。与其他基因型患者相比，同时遗传*1/*2和CT基因型的患者出现阴性临床结局和发生MACE的风险增加（22.73%对9.62%；OR 3.455；95%CI = [0.936 - 12.743]，p = 0.05722）。在CC/CT基因型携带者中也注意到有MACE风险增加的趋势。我们的结果支持单独或与C多态性联合存在与MACE风险增加相关的数据。结果还表明，C343T多态性的存在可能被视为接受氯吡格雷治疗患者发生MACE的独立预测因素。然而，这些结果是初步的，应在更多患者中得到证实。
