CYP2C19 and CES1 gene variants affecting clopidogrel metabolism in a South Asian population from Sri Lanka.

IF 1.9 4区医学 Q3 PHARMACOLOGY & PHARMACY

Pharmacogenomics Pub Date : 2025-01-14 DOI:10.1080/14622416.2025.2452835

Priyanga Ranasinghe, Pulasthi B Gunarathna, Hajanthy Jeyapragasam, Nirmala Sirisena, D P Bhagya Hendalage, Vajira H W Dissanayake

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引用次数: 0

Abstract

Aims: Clopidogrel exhibits substantial variability in therapeutic response, largely contributed by genetic factors. The pharmacogenomic variants data on clopidogrel metabolism in South Asians have been sparsely studied. This study explores the impact of CYP2C19 and CES1 gene variants on clopidogrel metabolism in Sri Lankans, revealing significant pharmacogenomic insights with broader implications for South Asians.

Materials & methods: Genotype data were filtered out from an anonymized database of 690 Sri Lankans, and minor allele frequencies (MAFs) were calculated. Five variants of CYP2C19 and one variant of CES1 gene were studied.

Results: Among the five CYP2C19 variants studied, rs12769205 (A>G) and rs4244285 (G>A) had the highest MAF of 42.1% and 42.0%, respectively. The CES1 variant rs71647871 (C>T) showed a MAF of 0.2%. Sri Lankans exhibited significantly higher MAFs for key variants compared to populations such as Europeans, African Americans, and East Asians (p < 0.05).

Conclusion: Given that South Asians share genetic similarities, these findings suggest that a substantial proportion of the region's population may also be poor responders to clopidogrel, increasing the risk of adverse outcomes. This highlights the importance of genotype-guided antiplatelet therapy, which could improve clinical outcomes across South Asia amidst rising cardiovascular disease rates.

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斯里兰卡南亚人群中影响氯吡格雷代谢的 CYP2C19 和 CES1 基因变异。

目的：氯吡格雷在治疗反应上表现出很大的变异性，主要是由遗传因素造成的。南亚人氯吡格雷代谢的药物基因组变异数据研究很少。本研究探讨了CYP2C19和CES1基因变异对斯里兰卡人氯吡格雷代谢的影响，揭示了对南亚人具有更广泛意义的重要药物基因组学见解。材料与方法：从690名斯里兰卡人的匿名数据库中筛选基因型数据，并计算次要等位基因频率（MAFs）。研究了CYP2C19基因的5个变异和CES1基因的1个变异。结果：在所研究的5个CYP2C19变异中，rs12769205 （A>G）和rs4244285 （G>A）的MAF最高，分别为42.1%和42.0%。CES1变异rs71647871 （C>T）的MAF为0.2%。与欧洲人、非裔美国人和东亚人相比，斯里兰卡人在关键变异上表现出明显更高的maf (p结论：鉴于南亚人具有遗传相似性，这些发现表明，该地区相当大比例的人口也可能对氯吡格雷反应不良，增加了不良后果的风险。这突出了基因型引导的抗血小板治疗的重要性，它可以改善南亚心血管疾病发病率上升的临床结果。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Pharmacogenomics 医学-药学

CiteScore

3.40

自引率

9.50%

发文量

审稿时长

4-8 weeks

期刊介绍： Pharmacogenomics (ISSN 1462-2416) is a peer-reviewed journal presenting reviews and reports by the researchers and decision-makers closely involved in this rapidly developing area. Key objectives are to provide the community with an essential resource for keeping abreast of the latest developments in all areas of this exciting field. Pharmacogenomics is the leading source of commentary and analysis, bringing you the highest quality expert analyses from corporate and academic opinion leaders in the field.