Clopidogrel is a widely prescribed prodrug that requires activation via specific pharmacogenes to exert its anti-platelet function. Genetic variations in the genes encoding its transporter, metabolizing enzymes, and target receptor lead to variability in its activation and platelet inhibition and, consequently, its efficacy. This variability increases the risk of secondary cardiovascular events, and therefore, some variations have been utilized as genetic biomarkers when prescribing clopidogrel. Our study examined clopidogrel-related genes (CYP2C19, ABCB1, PON1, and P2Y12R) in a cohort of 298 healthy Emiratis individuals. The study used whole exome sequencing (WES) data to comprehensively analyze pertinent variations of these genes, including their minor allele frequencies, haplotype distribution, and their resulting phenotypes. Our data shows that approximately 37% (n = 119) of the cohort are likely to benefit from the use of alternative anti-platelet drugs due to their classification as intermediate or poor CYP2C19 metabolizers. Additionally, more than 50% of the studied cohort exhibited variants in ABCB1, PON1, and P2YR12 genes, potentially influencing clopidogrel’s transport, enzymatic clearance, and receptor performance. Recognizing these alleles and genotype frequencies may explain the clinical differences in medication response across different ethnicities and predict adverse events. Our findings underscore the need to consider genetic variations in prescribing clopidogrel, with potential implications for implementing personalized anti-platelet therapy among Emiratis based on their genetic profiles.

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影响阿联酋人群氯吡格雷生物激活和反应的遗传变异的多样性和临床意义

氯吡格雷是一种广泛使用的前药，需要通过特定的药物基因激活才能发挥其抗血小板功能。编码其转运蛋白、代谢酶和靶受体的基因的遗传变异导致其激活和血小板抑制的变异，从而导致其功效的变异。这种变异性增加了继发性心血管事件的风险，因此，在开氯吡格雷处方时，一些变异被用作遗传生物标志物。我们的研究检查了 298 名健康阿联酋人的队列中的氯吡格雷相关基因（CYP2C19、ABCB1、PON1 和 P2Y12R）。该研究使用全外显子组测序（WES）数据来全面分析这些基因的相关变异，包括它们的次要等位基因频率、单倍型分布及其产生的表型。我们的数据显示，大约 37% (n = 119) 的队列可能受益于替代抗血小板药物的使用，因为它们被归类为中等或较差的 CYP2C19 代谢者。此外，超过 50% 的研究群体表现出 ABCB1、PON1 和 P2YR12 基因变异，可能影响氯吡格雷的转运、酶清除和受体性能。认识这些等位基因和基因型频率可以解释不同种族药物反应的临床差异并预测不良事件。我们的研究结果强调，在开具氯吡格雷处方时需要考虑遗传变异，这对根据阿联酋人的遗传特征实施个性化抗血小板治疗具有潜在影响。