Pharmacogenomics implementation in cardiovascular disease in a highly diverse population: initial findings and lessons learned from a pilot study in United Arab Emirates.

Autor: Al-Mahayri ZN; Department of Genetics and Genomics, College of Medicine and Health Sciences, United Arab Emirates University, P.O. Box: 15551, Al-Ain, United Arab Emirates., Khasawneh LQ; Department of Genetics and Genomics, College of Medicine and Health Sciences, United Arab Emirates University, P.O. Box: 15551, Al-Ain, United Arab Emirates., Alqasrawi MN; Department of Genetics and Genomics, College of Medicine and Health Sciences, United Arab Emirates University, P.O. Box: 15551, Al-Ain, United Arab Emirates., Altoum SM; Department of Genetics and Genomics, College of Medicine and Health Sciences, United Arab Emirates University, P.O. Box: 15551, Al-Ain, United Arab Emirates., Jamil G; Department of Medicine, Tawam Hospital, Al-Ain, United Arab Emirates., Badawi S; Department of Genetics and Genomics, College of Medicine and Health Sciences, United Arab Emirates University, P.O. Box: 15551, Al-Ain, United Arab Emirates., Hamza D; Department of Genetics and Genomics, College of Medicine and Health Sciences, United Arab Emirates University, P.O. Box: 15551, Al-Ain, United Arab Emirates., George L; Nursing Department, Tawam Hospital, Al-Ain, United Arab Emirates., AlZaabi A; Department of Medicine, Tawam Hospital, Al-Ain, United Arab Emirates., Ouda H; The Heart Medical Center, Al-Ain, United Arab Emirates., Al-Maskari F; Zayed Centre for Health Sciences, United Arab Emirates University, Al-Ain, United Arab Emirates.; Public Health Institute, College of Medicine and Health Sciences, United Arab Emirates University, Al-Ain, United Arab Emirates., AlKaabi J; Department of Internal Medicine, College of Medicine and Health Sciences, United Arab Emirates University, Al-Ain, United Arab Emirates., Patrinos GP; Department of Genetics and Genomics, College of Medicine and Health Sciences, United Arab Emirates University, P.O. Box: 15551, Al-Ain, United Arab Emirates.; Zayed Centre for Health Sciences, United Arab Emirates University, Al-Ain, United Arab Emirates.; School of Health Sciences, Department of Pharmacy, Laboratory of Pharmacogenomics and Individualized Therapy, University of Patras, Patras, Greece., Ali BR; Department of Genetics and Genomics, College of Medicine and Health Sciences, United Arab Emirates University, P.O. Box: 15551, Al-Ain, United Arab Emirates. bassam.ali@uaeu.ac.ae.; Zayed Centre for Health Sciences, United Arab Emirates University, Al-Ain, United Arab Emirates. bassam.ali@uaeu.ac.ae.
Jazyk: angličtina
Zdroj: Human genomics [Hum Genomics] 2022 Sep 25; Vol. 16 (1), pp. 42. Date of Electronic Publication: 2022 Sep 25.
DOI: 10.1186/s40246-022-00417-9
Abstrakt: Background: Pharmacogenomic (PGx) testing has proved its utility and cost-effectiveness for some commonly prescribed cardiovascular disease (CVD) medications. In addition, PGx-guided dosing guidelines are now available for multiple CVD drugs, including clopidogrel, warfarin, and statins. The United Arab Emirates (UAE) population is diverse and multiethnic, with over 150 nationalities residing in the country. PGx-testing is not part of the standard of care in most global healthcare settings, including the UAE healthcare system. The first pharmacogenomic implementation clinical study in CVD has been approved recently, but multiple considerations needed evaluation before commencing. The current report appraises the PGx-clinical implementation procedure and the potential benefits of pursuing PGx-implementation initiatives in the UAE with global implications.
Methods: Patients prescribed one or more of the following drugs: clopidogrel, atorvastatin, rosuvastatin, and warfarin, were recruited. Genotyping selected genetic variants at genes interacting with the study drugs was performed by real-time PCR.
Results: For the current pilot study, 160 patients were recruited. The genotypes and inferred haplotypes, diplotypes, and predicted phenotypes revealed that 11.9% of the participants were poor CYP2C19 metabolizers, 35% intermediate metabolizers, 28.1% normal metabolizers, and 25% rapid or ultrarapid metabolizers. Notably, 46.9% of our cohort should receive a recommendation to avoid using clopidogrel or consider an alternative medication. Regarding warfarin, only 20% of the participants exhibited reference alleles at VKORC1-1639G > A, CYP2C9*2, and CYP2C9*3, leaving 80% with alternative genotypes at any of the two genes that can be integrated into the warfarin dosing algorithms and can be used whenever the patient receives a warfarin prescription. For statins, 31.5% of patients carried at least one allele at the genotyped SLCO1B1 variant (rs4149056), increasing their risk of developing myopathy. 96% of our cohort received at least one PGx-generated clinical recommendation for the studied drugs.
Conclusion: The current pilot analysis verified the feasibility of PGx-testing and the unforeseen high frequencies of patients currently treated with suboptimal drug regimens, which may potentially benefit from PGx testing.
(© 2022. The Author(s).)
Databáze: MEDLINE
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