Hypertension in African Populations: Review andComputational Insights

Abstract

Hypertension (HTN) is a persistent public health problem affecting approximately 1.3 billion  individuals globally. Treatment-resistant hypertension (TRH) is defined as high blood pressure (BP)  in a hypertensive patient that remains above goal despite use of ≥3 antihypertensive agents of  different classes including a diuretic. Despite a plethora of treatment options available, only 31.0% of  individuals have their HTN controlled. Interindividual genetic variability to drug response might  explain this disappointing outcome because of genetic polymorphisms. Additionally, the poor  knowledge of pathophysiological mechanisms underlying hypertensive disease and the long-term  interaction of antihypertensive drugs with blood pressure control mechanisms further aggravates  the problem. Furthermore, in Africa, there is a paucity of pharmacogenomic data on the treatment of  resistant hypertension. Therefore, identification of genetic signals having the potential to predict the  response of a drug for a given individual in an African population has been the subject of intensive  investigation. In this review, we aim to systematically extract and discuss African evidence on the  genetic variation, and pharmacogenomics towards the treatment of HTN. Furthermore, in silico  methods are utilized to elucidate biological processes that will aid in identifying novel drug targets  for the treatment of resistant hypertension in an African population. To provide an expanded view of  genetic variants associated with the development of HTN, this study was performed using publicly  available databases such as PubMed, Scopus, Web of Science, African Journal Online, PharmGKB  searching for relevant papers between 1984 and 2020. A total of 2784 articles were reviewed, and  only 42 studies were included following the inclusion criteria. Twenty studies reported associations  with HTN and genes such as AGT (rs699), ACE (rs1799752), NOS3 (rs1799983), MTHFR (rs1801133),  AGTR1 (rs5186), while twenty-two studies did not show any association within the African population. Thereafter, an in silico predictive approach was utilized to identify several genes including  CLCNKB, CYPB11B2, SH2B2, STK9, and TBX5 which may act as potential drug targets because  they are involved in pathways known to influence blood pressure. Next, co-expressed genes were  identified as they are controlled by the same transcriptional regulatory program and may potentially  be more effective as multiple drug targets in the treatment regimens for HTN. Genes belonging to the  co-expressed gene cluster, ACE, AGT, AGTR1, AGTR2, and NOS3 as well as CSK and ADRG1 showed  enrichment of G-protein-coupled receptor activity, the classical targets of drug discovery, which  mediate cellular signaling processes. The latter is of importance, as the targeting of co-regulatory gene clusters will allow for the development of more effective HTN drug targets that could decrease  the prevalence of both controlled and TRH.