Department of Pharm.D, L. M. College of Pharmacy, Ahmedabad, Gujarat, India.
Department of Pharmacology, L. M. College of Pharmacy, Ahmedabad, Gujarat, India.
Indian J Pharmacol. 2023 Jan-Feb;55(1):27-33. doi: 10.4103/ijp.ijp_706_22.
Human cytochrome p450 enzymes play an important role in the metabolism of various substances. The CYP2C subfamily consists of various important drug-metabolizing enzymes such as CYP2C9 and CYP2C19. The objectives of the study include the determination of the frequency of genetic variants (CYP2C92, CYP2C93, and CYP2C192) of selected enzymes using allele-specific polymerase chain reaction (ASPCR) and its comparison with Indian as well as global past frequencies. We also aimed to study the impact of genetic mutation on clopidogrel efficacy and compare the efficacies between patients with and without CYP2C192 genetic variant.
In this study, the prevalence of variants CYP2C192, CYP2C92, and CYP2C93, the most popular variants of the respective enzymes, was determined using the ASPCR method. The correlation between the CYP2C192 variant and the antiplatelet activity of clopidogrel was studied using platelet aggregation assay (PAA).
The determined frequencies of CYP2C192, CYP2C92, and CYP2C93 are 46%, 9%, and 12%. These frequencies are indicative of homozygous as well as heterozygous mutations. Reduced clopidogrel efficacy was observed in patients with a heterozygous mutation of CYP2C192 variant.
The observed frequencies are not significantly different from that observed in earlier reported studies conducted across India and the world. Antiplatelet activity, as measured using the PAA method, was significantly lesser in patients having the CYP2C192 variant. The therapy failure in these patients can lead to serious cardiovascular consequences, and we propose determining the presence of the CYP2C192 variant before initiation of clopidogrel therapy.
人类细胞色素 P450 酶在各种物质的代谢中起着重要作用。CYP2C 亚家族由各种重要的药物代谢酶组成，如 CYP2C9 和 CYP2C19。本研究的目的包括使用等位基因特异性聚合酶链反应（ASPCR）确定选定酶的遗传变异（CYP2C92、CYP2C93 和 CYP2C192）的频率，并将其与印度及全球以往的频率进行比较。我们还旨在研究遗传突变对氯吡格雷疗效的影响，并比较具有和不具有 CYP2C192 遗传变异的患者之间的疗效。
在这项研究中，使用 ASPCR 方法确定了各自酶中最常见的变异 CYP2C192、CYP2C92 和 CYP2C93 的流行率。使用血小板聚集测定（PAA）研究 CYP2C192 变异与氯吡格雷抗血小板活性之间的相关性。
确定的 CYP2C192、CYP2C92 和 CYP2C93 的频率分别为 46%、9%和 12%。这些频率表明存在纯合和杂合突变。在 CYP2C192 变异的杂合突变患者中观察到氯吡格雷疗效降低。
观察到的频率与在印度和世界各地进行的早期报告研究中观察到的频率没有显著差异。使用 PAA 方法测量的抗血小板活性在具有 CYP2C192 变异的患者中明显较低。这些患者的治疗失败可能导致严重的心血管后果，我们建议在开始氯吡格雷治疗之前确定 CYP2C192 变异的存在。
