Antihypertensives associated adverse events: a review of mechanisms and pharmacogenomic biomarkers available evidence in multi-ethnic populations.

Autor:	Altoum SM; Department of Genetics and Genomics, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates., Al-Mahayri ZN; Department of Genetics and Genomics, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates., Ali BR; Department of Genetics and Genomics, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates.; ASPIRE Precision Medicine Research Institute Abu Dhabi, United Arab Emirates University, Al Ain, United Arab Emirates.
Jazyk:	angličtina
Zdroj:	Frontiers in pharmacology [Front Pharmacol] 2023 Dec 01; Vol. 14, pp. 1286494. Date of Electronic Publication: 2023 Dec 01 (Print Publication: 2023).
DOI:	10.3389/fphar.2023.1286494
Abstrakt:	Hypertension remains a significant health burden worldwide, re-emphasizing the outstanding need for more effective and safer antihypertensive therapeutic approaches. Genetic variation contributes significantly to interindividual variability in treatment response and adverse events, suggesting pharmacogenomics as a major approach to optimize such therapy. This review examines the molecular mechanisms underlying antihypertensives-associated adverse events and surveys existing research on pharmacogenomic biomarkers associated with these events. The current literature revealed limited conclusive evidence supporting the use of genetic variants as reliable indicators of antihypertensive adverse events. However, several noteworthy associations have emerged, such as 1) the role of ACE variants in increasing the risk of multiple adverse events, 2) the bradykinin pathway's involvement in cough induced by ACE inhibitors, and 3) the impact of CYP2D6 variants on metoprolol-induced bradycardia. Nonetheless, challenges persist in identifying biomarkers for adverse events across different antihypertensive classes, sometimes due to the rarity of certain events, such as ACE inhibitors-induced angioedema. We also highlight the main limitations of previous studies that warrant attention, including using a targeted gene approach with a limited number of tested variants, small sample sizes, and design issues such as overlooking doses or the time between starting treatment and the onset of adverse events. Addressing these challenges requires collaborative efforts and the integration of technological advancements, such as next-generation sequencing, which can significantly enhance research outcomes and provide the needed evidence. Furthermore, the potential combination of genomic biomarker identification and machine learning is a promising approach for tailoring antihypertensive therapy to individual patients, thereby mitigating the risk of developing adverse events. In conclusion, a deeper understanding of the mechanisms and the pharmacogenomics of adverse events in antihypertensive therapy will likely pave the way for more personalized treatment strategies to improve patient outcomes. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision. (Copyright © 2023 Altoum, Al-Mahayri and Ali.)
Databáze:	MEDLINE
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