Mugosa Snezana, Todorovic Zoran, Cukic Jelena, Sahman-Zaimovic Majda, Djordjevic Natasa
Faculty of Medicine, Department of Pharmacology, University of Montenegro, 81104 Podgorica, Montenegro.
Institute for Medicines and Medical Devices of Montenegro, 81104 Podgorica, Montenegro.
Open Life Sci. 2021 Feb 18;16(1):142-149. doi: 10.1515/biol-2021-0017. eCollection 2021.
Clopidogrel is an antiplatelet drug that displays significant interindividual variability in treatment response. Its bioavailability depends on the function of P-glycoprotein (P-gp), which is coded by a highly polymorphic gene. Thus, the aim of this study was to investigate the effect of genetic polymorphism on clopidogrel efficacy and safety and to determine the frequency distribution of its most common single nucleotide polymorphisms (SNPs) in 106 Montenegrin cardiology patients. Clopidogrel efficacy and safety were followed up during 1 year after hospitalization, with the lack of efficacy and adverse drug reactions observed in 11 (10.4%) and 8 patients (7.5%), respectively. Genotyping for SNPs rs1128503 (1236C > T), rs2032582 (2677G > A/T), and rs1045642 (3435C > T) was performed by the real-time PCR method, and the variant alleles were detected with the frequencies of 42.9, 44.8, and 52.8%, respectively. No significant association was observed between any of the examined genotypes and clopidogrel efficacy ( = 0.253) or safety ( = 0.424). Due to small sample size, co-treatment with other drugs, and other genetic factors not taken into account, we believe the absence of correlation between genotypes and indicators of clopidogrel efficacy and safety in this study should be apprehended conditionally, and that larger and better-controlled studies are warranted.
氯吡格雷是一种抗血小板药物，其治疗反应存在显著的个体间差异。其生物利用度取决于由高度多态性基因编码的P-糖蛋白（P-gp）的功能。因此，本研究的目的是调查基因多态性对氯吡格雷疗效和安全性的影响，并确定其最常见的单核苷酸多态性（SNP）在106例黑山心脏病患者中的频率分布。在住院后1年对氯吡格雷的疗效和安全性进行随访，分别有11例（10.4%）和8例（7.5%）患者出现疗效不佳和药物不良反应。采用实时PCR方法对SNP rs1128503（1236C>T）、rs2032582（2677G>A/T）和rs1045642（3435C>T）进行基因分型，检测到变异等位基因的频率分别为42.9%、44.8%和52.8%。在所检测的任何基因型与氯吡格雷疗效（P=0.253）或安全性（P=0.424）之间均未观察到显著关联。由于样本量小、与其他药物联合治疗以及未考虑其他遗传因素，我们认为本研究中基因型与氯吡格雷疗效和安全性指标之间缺乏相关性应谨慎看待，需要进行更大规模且控制更好的研究。
