Institute of Cardiology, Lithuanian University of Health Sciences, Sukileliu 15, LT 50103 Kaunas, Lithuania.
Department of Cardiology, Kaunas Hospital of the Lithuanian University of Health Sciences, Hipodromo 13, LT 45130 Kaunas, Lithuania.
Int J Mol Sci. 2024 May 15;25(10):5385. doi: 10.3390/ijms25105385.
The effectiveness of lipid-lowering therapies may be insufficient in high-risk cardiovascular patients and depends on the genetic variability of drug-metabolizing enzymes. Customizing statin therapy, including treatment with atorvastatin, may improve clinical outcomes. Currently, there is a lack of guidelines allowing the prediction of the therapeutic efficacy of lipid-lowering statin therapy. This study aimed to determine the effects of clinically significant gene variants of on atorvastatin therapy in patients with acute coronary syndromes. In total, 92 patients with a confirmed diagnosis of ST-elevation myocardial infarction (STEMI) or non-ST-elevation myocardial infarction (NSTEMI) were sequenced for target regions within the gene on the Illumina Miniseq system. The CYP2C19 poor metabolizer phenotype (carriers of , , and alleles) was detected in 29% of patients. These patients had significantly lower responses to treatment with atorvastatin than patients with the normal metabolizer phenotype. CYP2C19-metabolizing phenotype, patient age, and smoking increased the odds of undertreatment in patients (∆LDL-C (mmol/L) < 1). These results revealed that the CYP2C19 phenotype may significantly impact atorvastatin therapy personalization in patients requiring LDL lipid-lowering therapy.
降脂治疗的效果在心血管高危患者中可能不够,这取决于药物代谢酶的遗传变异性。定制他汀类药物治疗,包括阿托伐他汀治疗,可能改善临床结局。目前,缺乏允许预测降脂他汀类药物治疗疗效的指南。本研究旨在确定在急性冠脉综合征患者中,阿托伐他汀治疗的临床显著基因变异对 基因的影响。总共对 92 例经证实的 ST 段抬高型心肌梗死(STEMI)或非 ST 段抬高型心肌梗死(NSTEMI)患者的 Illumina Miniseq 系统内 基因的目标区域进行了测序。在 29%的患者中检测到 CYP2C19 弱代谢表型(携带 、 和 等位基因)。与正常代谢表型患者相比,这些患者对阿托伐他汀治疗的反应明显较低。CYP2C19 代谢表型、患者年龄和吸烟增加了患者治疗不足的几率(∆LDL-C(mmol/L)<1)。这些结果表明,CYP2C19 表型可能显著影响需要 LDL 降脂治疗的患者的阿托伐他汀治疗个体化。