Katsukunya Jonathan N, Soko Nyarai D, Naidoo Jashira, Rayner Brian, Blom Dirk, Sinxadi Phumla, Chimusa Emile R, Dandara Michelle, Dzobo Kevin, Jones Erika, Dandara Collet
Division of Human Genetics, Department of Pathology and Institute of Infectious Disease and Molecular Medicine (IDM), Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.
UCT/South African Medical Research Council (SAMRC) Platform for Pharmacogenomics Research and Translation Unit, University of Cape Town, Cape Town, South Africa.
Int J Hypertens. 2023 May 30;2023:9919677. doi: 10.1155/2023/9919677. eCollection 2023.
In Africa, the burden of hypertension has been rising at an alarming rate for the last two decades and is a major cause for cardiovascular disease (CVD) mortality and morbidity. Hypertension is characterised by elevated blood pressure (BP) ≥ 140/90 mmHg. Current hypertension guidelines recommend the use of antihypertensives belonging to the following classes: calcium channel blockers (CCB), angiotensin converting inhibitors (ACEI), angiotensin receptor blockers (ARB), diuretics, -blockers, and mineralocorticoid receptor antagonists (MRAs), to manage hypertension. Still, a considerable number of hypertensives in Africa have their BP uncontrolled due to poor drug response and remain at the risk of CVD events. Genetic factors are a major contributing factor, accounting for 20% to 80% of individual variability in therapy and poor response. Poor response to antihypertensive drug therapy is characterised by elevated BPs and occurrence of adverse drug reactions (ADRs). As a result, there have been numerous studies which have examined the role of genetic variation and its influence on antihypertensive drug response. These studies are predominantly carried out in non-African populations, including Europeans and Asians, with few or no Africans participating. It is important to note that the greatest genetic diversity is observed in African populations as well as the highest prevalence of hypertension. As a result, this warrants a need to focus on how genetic variation affects response to therapeutic interventions used to manage hypertension in African populations. In this paper, we discuss the implications of genetic diversity in genes, and chromosome 12q loci on hypertension susceptibility and response to antihypertensive therapy. We show that African populations are poorly explored genetically, and for the few characterised genes, they exhibit qualitative and quantitative differences in the profile of pharmacogene variants when compared to other ethnic groups. We conclude by proposing prioritization of pharmacogenetics research in Africa and possible adoption of pharmacogenetic-guided therapies for hypertension in African patients. Finally, we outline the implications, challenges, and opportunities these studies present for populations of non-European descent.
在非洲,过去二十年来高血压负担一直以惊人的速度上升,是心血管疾病(CVD)死亡率和发病率的主要原因。高血压的特征是血压(BP)升高≥140/90 mmHg。当前的高血压指南建议使用以下几类抗高血压药物:钙通道阻滞剂(CCB)、血管紧张素转换酶抑制剂(ACEI)、血管紧张素受体阻滞剂(ARB)、利尿剂、β受体阻滞剂和盐皮质激素受体拮抗剂(MRA)来治疗高血压。然而,由于药物反应不佳,非洲仍有相当数量的高血压患者血压未得到控制,仍然面临心血管疾病事件的风险。遗传因素是一个主要促成因素,占个体治疗差异和不良反应的20%至80%。抗高血压药物治疗反应不佳的特征是血压升高和药物不良反应(ADR)的发生。因此,有许多研究探讨了基因变异的作用及其对抗高血压药物反应的影响。这些研究主要在非非洲人群中进行,包括欧洲人和亚洲人,很少或没有非洲人参与。需要注意的是,非洲人群中观察到的遗传多样性最大,高血压患病率也最高。因此,有必要关注基因变异如何影响非洲人群中用于治疗高血压的治疗干预措施的反应。在本文中,我们讨论了基因和12号染色体q位点的遗传多样性对高血压易感性和抗高血压治疗反应的影响。我们表明,非洲人群在遗传方面研究不足,对于少数已鉴定的基因,与其他种族群体相比,它们在药物基因变异谱中表现出定性和定量的差异。我们通过提议优先开展非洲的药物遗传学研究以及可能对非洲高血压患者采用药物遗传学指导的治疗方法来得出结论。最后,我们概述了这些研究对非欧洲血统人群的影响、挑战和机遇。