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. 2024 Jan;26(1):e3634.
doi: 10.1002/jgm.3634. Epub 2023 Nov 20.

Pharmacogenomic evaluation of CYP2C19 alleles linking low clopidogrel response and the risk of acute coronary syndrome in Indians

Keshavamurthy Ganapathy Bhat  1 , Ratheesh Kumar Janardhana Pillai  1 , Heemanshu Lodhi  1 , Vivek Singh Guleria  1 , Anil Kumar Abbot  1 , Love Gupta  2 , Garima Rastogi  2 , Anuka Sharma  2 , Zafar Mohammed  3 , Varun Sharma  2
Affiliations

Pharmacogenomic evaluation of CYP2C19 alleles linking low clopidogrel response and the risk of acute coronary syndrome in Indians

Keshavamurthy Ganapathy Bhat et al. J Gene Med. 2024 Jan.

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: CYP2C19; acute coronary syndrome; clopidogrel; metabolizers; pharmacogenomics.

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