Federal State Budgetary Educational Institution of Further Professional Education "Russian Medical Academy of Continuous Professional Education", Ministry of Healthcare of the Russian Federation, Barrikadnaja Street, 2/1, Moscow, Russia, 125993.
Lomonosov Moscow State University, Moscow, Russia.
Mol Biol Rep. 2019 Aug;46(4):4195-4199. doi: 10.1007/s11033-019-04871-y. Epub 2019 May 17.
The objective of this study was to determine the impact of polymorphism of CYP3A subfamily isoenzymes (allelic variants of CYP3A422 and CYP3A53) on the efficacy clopidogrel in patients with an acute coronary syndrome (ACS), who have undergone percutaneous coronary intervention (PCI). Platelet activity was determined on a VerifyNow P2Y12 test system in 81 patients with ACS aged 37-91 who had PCI. The activity of CYP3A4/5 was expressed as the ratio of the concentrations of cortisol and 6β-hydroxycortisol was performed by using high performance liquid chromatography. Genotyping was performed by using real-time polymerase real-time chain reaction. The frequencies for the CYP3A5 gene, rs 776746, were identified as follows: 77 (95.1%)-CC, 4 (4.9%)-CT; the allele frequencies by loci for the CYP3A4, rs rs35599367, were as follows: 78 (96.3%)-GG, 3 (3.7%)-AG. There was no statistically significant genotype-dependent difference between the presence of a minor T and G alleles and the presence of clopidogrel resistance (OR 3.53; 95% CI 0.46-26.94; p = 0.233 and p = 0.443, respectively). The average level of the metabolic relationship (6β-hydroxycortisol/cortisol) between the clopidogrel-resistant group and the normal platelet reactivity group was not statistically significantly different: 3.3 ± 2.8 versus 3.2 ± 3.2; p = 0.947. So, the activity of CYP3A4/5 was not related to platelet aggregation rates in this model. Genotyping and phenotyping CYP3A4\CYP3A5 does not predict the antiplatelet effect of clopidogrel. More extensive research is required to establish their clinical relevance.
本研究旨在确定 CYP3A 亚家族同工酶（CYP3A422 和 CYP3A53 等位基因变异）多态性对接受经皮冠状动脉介入治疗（PCI）的急性冠状动脉综合征（ACS）患者氯吡格雷疗效的影响。在 81 名年龄 37-91 岁接受 PCI 的 ACS 患者中，使用 VerifyNow P2Y12 测试系统测定血小板活性。CYP3A4/5 的活性通过使用高效液相色谱法测定皮质醇和 6β-羟基皮质醇浓度的比值来表示。通过实时聚合酶链反应实时进行基因分型。CYP3A5 基因 rs776746 的频率鉴定如下：77（95.1%）-CC、4（4.9%）-CT；CYP3A4 基因 rs35599367 的等位基因频率如下：78（96.3%）-GG、3（3.7%）-AG。在存在小 T 和 G 等位基因和氯吡格雷抵抗的情况下，基因型依赖性差异无统计学意义（OR 3.53；95%CI 0.46-26.94；p=0.233 和 p=0.443）。氯吡格雷抵抗组和正常血小板反应组之间代谢关系（6β-羟基皮质醇/皮质醇）的平均水平无统计学差异：3.3±2.8 与 3.2±3.2；p=0.947。因此，在该模型中，CYP3A4/5 的活性与血小板聚集率无关。CYP3A4/CYP3A5 的基因分型和表型不能预测氯吡格雷的抗血小板作用。需要进行更广泛的研究以确定其临床相关性。
