Soko Nyarai D, Masimirembwa Collen, Dandara Collet
1 Pharmacogenetics Research Group, Division of Human Genetics, Department of Pathology, Faculty of Health Sciences, and University of Cape Town , Cape Town, South Africa .
2 African Institute of Biomedical Science and Technology (AiBST) , Wilkins Hospital, Harare, Zimbabwe .
OMICS. 2016 Sep;20(9):498-509. doi: 10.1089/omi.2016.0114.
The incidence of cardiovascular diseases (CVDs) in African populations residing in the African continent is on the rise fueled by both a steady increase in CVD risk factors and comorbidities such as human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS), tuberculosis, and parasitic diseases such as bilharzia. Statins are recommended together with lifestyle changes in the treatment of hypercholesterolemia and overall reduction of cardiovascular events. Rosuvastatin in particular is an attractive candidate in the management of CVDs in African populations often plagued with multimorbidities owing to both its potency and low drug-to-drug interaction potential. In this expert review, we describe the pharmacogenetics of rosuvastatin and how it may instrumentally affect the African populations. We describe polymorphisms in the candidate genes, ABCG2, SLCO1B1, CYP2C9, APOE, PCSK9, LDLR, LPA, and HMGCR, and their role in the potency and safety of rosuvastatin therapy. We report on qualitative and quantitative differences in the distribution of genetic variants that affect efficacy and toxicity of rosuvastatin. These differences are observed across world populations (Caucasian, European, and Asian) as well as within African populations. Finally, we advocate for extensive pharmacogenetic studies in African populations that take into account the genetic diversity of intra-African ethnic groups and the genetic differences between African populations and other global populations, with a collaborative and collective aim to provide effective and safe use of rosuvastatin in management of CVD in Africa. Our key thesis presented in this innovation field analysis is that rosuvastatin precision medicine can serve as a veritable Glocal (Global and Local) model to offer pharmacogenetic-guided optimal therapeutics for the public in both developing and developed regions of the world.
由于心血管疾病（CVD）风险因素和合并症（如人类免疫缺陷病毒/获得性免疫缺陷综合征（HIV/AIDS）、结核病以及血吸虫病等寄生虫病）持续增加，居住在非洲大陆的非洲人群中CVD的发病率正在上升。在治疗高胆固醇血症和全面降低心血管事件方面，推荐他汀类药物并结合生活方式改变。特别是瑞舒伐他汀，由于其效力和低药物相互作用潜力，在经常受多种疾病困扰的非洲人群的CVD管理中是一个有吸引力的选择。在本专家综述中，我们描述了瑞舒伐他汀的药物遗传学及其如何对非洲人群产生重要影响。我们描述了候选基因ABCG2、SLCO1B1、CYP2C9、APOE、PCSK9、LDLR、LPA和HMGCR中的多态性，以及它们在瑞舒伐他汀治疗的效力和安全性中的作用。我们报告了影响瑞舒伐他汀疗效和毒性的基因变异分布的定性和定量差异。这些差异在世界人群（高加索人、欧洲人和亚洲人）以及非洲人群内部都有观察到。最后，我们主张在非洲人群中进行广泛的药物遗传学研究，考虑到非洲内部种族群体的遗传多样性以及非洲人群与其他全球人群之间的遗传差异，共同目标是在非洲CVD管理中有效且安全地使用瑞舒伐他汀。我们在本创新领域分析中提出的关键论点是，瑞舒伐他汀精准医学可以作为一个名副其实的全球本地化（全球和本地）模式，为世界发展中地区和发达地区的公众提供药物遗传学指导的最佳治疗方法。
