Hypertension in African Populations: Review and Computational Insights

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dc.contributor.authorMabhida, Sihle E.
dc.contributor.authorMashatola, Lebohang
dc.contributor.authorKaur, Mandeep
dc.contributor.authorSharma, Jyoti R
dc.contributor.authorApalata, Teke
dc.contributor.authorMuhamed, Babu
dc.contributor.authorBenjeddou, Mongi
dc.contributor.authorJohnson, Rabia
dc.date.accessioned2021-10-15T07:18:54Z
dc.date.available2021-10-15T07:18:54Z
dc.date.issued2021-04-06
dc.date.updated2021-04-23T13:31:25Z
dc.description.abstractHypertension (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 <i>AGT</i> (rs699), <i>ACE</i> (rs1799752), <i>NOS3</i> (rs1799983), <i>MTHFR</i> (rs1801133), <i>AGTR1</i> (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 <i>CLCNKB</i>, <i>CYPB11B2</i>, <i>SH2B2, STK9</i>, and <i>TBX5</i> 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, <i>ACE, AGT, AGTR1, AGTR2</i>, and <i>NOS3</i> as well as <i>CSK</i> and <i>ADRG1</i> 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.en_US
dc.identifier10.3390/genes12040532
dc.identifier.apacitationMabhida, Sihle E., Mashatola, L., Kaur, M., Sharma, J. R., Apalata, T., Muhamed, B., ... Johnson, R. (2021). Hypertension in African Populations: Review and Computational Insights. <i>Genes</i>, 12(4), 532. http://hdl.handle.net/11427/35256en_ZA
dc.identifier.chicagocitationMabhida, Sihle E., Lebohang Mashatola, Mandeep Kaur, Jyoti R Sharma, Teke Apalata, Babu Muhamed, Mongi Benjeddou, and Rabia Johnson "Hypertension in African Populations: Review and Computational Insights." <i>Genes</i> 12, 4. (2021): 532. http://hdl.handle.net/11427/35256en_ZA
dc.identifier.citationMabhida, Sihle E., Mashatola, L., Kaur, M., Sharma, J.R., Apalata, T., Muhamed, B., Benjeddou, M. & Johnson, R. et al. 2021. Hypertension in African Populations: Review and Computational Insights. <i>Genes.</i> 12(4):532. http://hdl.handle.net/11427/35256en_ZA
dc.identifier.ris TY - Journal Article AU - Mabhida, Sihle E. AU - Mashatola, Lebohang AU - Kaur, Mandeep AU - Sharma, Jyoti R AU - Apalata, Teke AU - Muhamed, Babu AU - Benjeddou, Mongi AU - Johnson, Rabia AB - 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 <i>AGT</i> (rs699), <i>ACE</i> (rs1799752), <i>NOS3</i> (rs1799983), <i>MTHFR</i> (rs1801133), <i>AGTR1</i> (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 <i>CLCNKB</i>, <i>CYPB11B2</i>, <i>SH2B2, STK9</i>, and <i>TBX5</i> 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, <i>ACE, AGT, AGTR1, AGTR2</i>, and <i>NOS3</i> as well as <i>CSK</i> and <i>ADRG1</i> 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. DA - 2021-04-06 DB - OpenUCT DP - University of Cape Town IS - 4 J1 - Genes LK - https://open.uct.ac.za PY - 2021 T1 - Hypertension in African Populations: Review and Computational Insights TI - Hypertension in African Populations: Review and Computational Insights UR - http://hdl.handle.net/11427/35256 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/35256
dc.identifier.vancouvercitationMabhida Sihle E, Mashatola L, Kaur M, Sharma JR, Apalata T, Muhamed B, et al. Hypertension in African Populations: Review and Computational Insights. Genes. 2021;12(4):532. http://hdl.handle.net/11427/35256.en_ZA
dc.language.isoenen_US
dc.publisher.departmentDepartment of Medicineen_US
dc.publisher.facultyFaculty of Health Sciencesen_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_US
dc.sourceGenesen_US
dc.source.journalissue4en_US
dc.source.journalvolume12en_US
dc.source.pagination532en_US
dc.source.urihttps://www.mdpi.com/journal/genes
dc.titleHypertension in African Populations: Review and Computational Insightsen_US
dc.typeJournal Articleen_US
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