Association between CYP3A4/CYP3A5 genetic polymorphisms and treatment outcomes of atorvastatin worldwide: is there enough research on the Egyptian population?

Maslub, Mohammed G., Radwan, Mahasen A., Daud, Nur Aizati Athirah and Sha’aban, Abubakar ORCID: https://orcid.org/0000-0002-5491-9851 2023. Association between CYP3A4/CYP3A5 genetic polymorphisms and treatment outcomes of atorvastatin worldwide: is there enough research on the Egyptian population? European Journal of Medical Research 28 , 381. 10.1186/s40001-023-01038-1

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Abstract

Introduction: Atorvastatin is regarded as the most frequently prescribed statin worldwide for dyslipidemia. However, clinical response and risk of adverse effects to statin therapy are associated with genetic variations. Numerous research linked statins pharmacokinetics (PK) variations to genetic polymorphisms in cytochromes P450 (CYPs) metabolic enzymes. Objective: This article reviews the association between CYP3A4/5 genetic variations and response to atorvastatin therapy globally, which includes atorvastatin PK, and the risk for adverse reactions, with a hint to the Egyptians. Methods: Up to March 30, 2022, electronic medical databases like PubMed, Web of Science, MEDLINE, and Egyptian Knowledge Bank (EKB) were searched. All articles that highlighted the relationship between CYP3A4/5 genetic polymorphisms and atorvastatin efficacy/safety profile were included in this review. Results: Initially, 492 articles were retrieved after an exhaustive search. There were 24 articles included according to the inclusion criteria. Findings of association studies of CYP3A4/5 genetic polymorphisms with response to atorvastatin varied among different ethnicities. CYP3A4*1B was associated with better therapeutic outcomes after atorvastatin therapy in Chileans and vice versa in Americans. Caucasians with myalgia while using atorvastatin were at significant risk of suffering severe muscle damage if they were carriers of CYP3A5*3/*3. As far as we can report for the Egyptian population, the impact of CYP3A4/5 genetic variations on the response to atorvastatin therapy was understudied. Conclusion: More pharmacogenetic studies amongst diverse populations worldwide, like the Egyptian population, are necessary to detect further atorvastatin-gene interactions. Graphical Abstract:

Item Type:	Article
Date Type:	Published Online
Status:	Published
Schools:	Medicine
Additional Information:	License information from Publisher: LICENSE 1: URL: http://creativecommons.org/licenses/by/4.0/, Type: open-access
Publisher:	BioMed Central
Date of First Compliant Deposit:	28 September 2023
Date of Acceptance:	31 January 2023
Last Modified:	29 Sep 2023 06:19
URI:	https://orca.cardiff.ac.uk/id/eprint/162807

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