Muyambo, Sarudzai, Ndadza, Arinao, Soko, Nyarai D., Kruger, Bianca, Kadzirange, Gerard, Chimusa, Emile Rugamika, Masimirembwa, Collen M., Ntsekhe, Mpiko, Nhachi, Charles F.B. and Dandara, Collet (2022) Warfarin Pharmacogenomics for Precision Medicine in Real-Life Clinical Practice in Southern Africa: Harnessing 73 Variants in 29 Pharmacogenes. OMICS: A Journal of Integrative Biology, 26 (1). pp. 35-50. ISSN 1557-8100
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Abstract
Pharmacogenomics is universally relevant for worldwide modern therapeutics and yet needs further development in resource-limited countries. While there is an abundance of genetic association studies in controlled medical settings, there is a paucity of studies with a naturalistic design in real-life clinical practice in patients with comorbidities and under multiple drug treatment regimens. African patients are often burdened with communicable and noncommunicable comorbidities, yet the application of pharmacogenomics in African clinical settings remains limited. Using warfarin as a model, this study aims at minimizing gaps in precision/personalized medicine research in African clinical practice. We present, therefore, pharmacogenomic profiles of a cohort of 503 black Africans (n = 252) and Mixed Ancestry (n = 251) patients from Southern Africa, on warfarin and co-prescribed drugs in a naturalized noncontrolled environment. Seventy-three (n = 73) single nucleotide polymorphisms (SNPs) in 29 pharmacogenes were characterized using a combination of allelic discrimination, Sanger sequencing, restriction fragment length polymorphism, and Sequenom Mass Array. The common comorbidities were hypertension (43-46%), heart failure (39-45%), diabetes mellitus (18%), arrhythmia (25%), and HIV infection (15%). Accordingly, the most common co-prescribed drugs were antihypertensives, antiarrhythmic drugs, antidiabetics, and antiretroviral therapy. We observed marked variation in major pharmacogenes both at interethnic levels and within African subpopulations. The Mixed Ancestry group presented a profile of genetic variants reflecting their European, Asian, and African admixture. Precision medicine requires that African populations begin to capture their own pharmacogenetic SNPs as they cannot always infer with absolute certainty from Asian and European populations. In the current historical moment of the COVID-19 pandemic, we also underscore that the spectrum of drugs interacting with warfarin will likely increase, given the systemic and cardiovascular effects of COVID-19, and the anticipated influx of COVID-19 medicines in the near future. This observational clinical pharmacogenomics study of warfarin, together with past precision medicine research, collectively, lends strong support for incorporation of pharmacogenetic profiling in clinical settings in African patients for effective and safe administration of therapeutics.
| Item Type: | Article |
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| Additional Information: | Funding Information: Collection and initial processing of samples was funded through grant to S.M. from Bindura University of Science Education (BUSE). Genetic characterization was funded through grants to C.D. from the South African Medical Research Council (SAMRC) and National Research Foundation (NRF) of South Africa. The work by A.N. reported herein was made possible through the funding received from the SAMRC through its Division of Research Capacity Development under the Bongani Mayosi National Health Scholarship Programme from funding received from the Public Health Enhancement Fund/South African National Department of Health. The content hereof is the sole responsibility of the authors and does not necessarily represent the official views of the SAMRC or the funders. |
| Uncontrolled Keywords: | Africa, drug transporters, gene-drug interaction, genetic variation, personalized medicine, pharmacogenomics, warfarin |
| Subjects: | C400 Genetics |
| Department: | Faculties > Health and Life Sciences > Applied Sciences |
| Depositing User: | Rachel Branson |
| Date Deposited: | 02 Nov 2022 14:53 |
| Last Modified: | 02 Nov 2022 15:00 |
| URI: | https://nrl.northumbria.ac.uk/id/eprint/50517 |
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