Department of Cardiology, Army Hospital, Research and Referral, New Delhi, India.
NMC Genetics India Pvt. Ltd, Gurugram, Haryana, India.
J Gene Med. 2024 Jan;26(1):e3634. doi: 10.1002/jgm.3634. Epub 2023 Nov 20.
Clopidogrel is an antiplatelet drug widely prescribed to prevent atherothrombotic events in coronary artery disease patients. However, there is evidence to suggest that the effectiveness of clopidogrel varies owing to genetic diversity in CYP2C19. This heterogeneity in South Asians, who are also known to have high risk of cardiac events than other population groups, highlights the importance of investigating CYP2C19 variants to estimate the risk proportion in the groups.
Given the high prevalence and genetic heterogeneity, the population-based case control was conducted in a cohort of 1191 subjects comprising 645 acute coronary syndrome (ACS) cases (unstable angina, ST-elevation myocardial infarction, and non-ST-elevation myocardial infarction) and 546 healthy controls of South Asian Indian origin. The metabolization status of CYP2C19 was assessed using *2, *3 and *17 variants in the stated cohorts to determine the prevalence of metabolization and its association with phenotypes.
The results suggest a possible genetic association between studied CYP2C19 polymorphisms and ACS, since there was a higher proportion of intermediate and poor metabolizers present in the studied cohorts. The association analyses revealed that the *2 allele of CYP2C19 confers a significant risk for ACS, while the *17 allele provides protection.
These findings contribute to the understanding of CYP2C19 genetic variants and their impact on clopidogrel response in South Asian Indians. Additionally, they underline the significance of assessing CYP2C19 variations in patients receiving clopidogrel therapy in order to improve therapeutic outcomes.
氯吡格雷是一种广泛用于预防冠心病患者动脉血栓事件的抗血小板药物。然而，有证据表明，由于 CYP2C19 的遗传多样性，氯吡格雷的有效性存在差异。南亚人群的这种异质性也表明，他们发生心脏事件的风险高于其他人群，这突出了研究 CYP2C19 变异体以估计该人群中风险比例的重要性。
鉴于高患病率和遗传异质性，在一个由 1191 名受试者组成的队列中进行了基于人群的病例对照研究，其中包括 645 名急性冠脉综合征（ACS）病例（不稳定型心绞痛、ST 段抬高型心肌梗死和非 ST 段抬高型心肌梗死）和 546 名南亚印度裔健康对照者。使用*2、3 和17 变体在所述队列中评估 CYP2C19 的代谢状态，以确定代谢状态的流行率及其与表型的关联。
研究结果表明，在所研究的 CYP2C19 多态性与 ACS 之间可能存在遗传关联，因为在研究队列中存在更多的中间代谢和不良代谢者。关联分析表明，CYP2C19 的2 等位基因赋予 ACS 的显著风险，而17 等位基因提供保护。
这些发现有助于了解 CYP2C19 遗传变异及其对南亚印度人氯吡格雷反应的影响。此外，它们强调了在接受氯吡格雷治疗的患者中评估 CYP2C19 变异以改善治疗结果的重要性。
