{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T19:58:50Z","timestamp":1782849530414,"version":"3.54.5"},"reference-count":21,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T00:00:00Z","timestamp":1776729600000},"content-version":"vor","delay-in-days":110,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["International Journal of Hypertension"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      In Sub\u2010Saharan Africa, the escalating burden of hypertension converges with persistent malaria endemicity, creating a complex clinical challenge marked by increasing rates of resistance to first\u2010line antihypertensive therapies, particularly angiotensin\u2010converting enzyme inhibitors (ACEIs) and Angiotensin II receptor blockers (ARBs). The molecular mechanisms underpinning this therapeutic failure remain elusive.\n                      <jats:italic>Rac1<\/jats:italic>\n                      , a Rho GTPase regulating both cardiovascular function and erythrocyte biology, presents a compelling molecular link between these comorbidities, yet its regulatory architecture in this context is uncharacterized.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We conducted a comprehensive\n                      <jats:italic>in silico<\/jats:italic>\n                      analysis of the human\n                      <jats:italic>Rac1<\/jats:italic>\n                      promoter region (\u22122000 to +500\u2009bp relative to the transcription start site) using biomaRt, BSgenome, and the JASPAR2022 database, anchored to the GRCh38\/hg38 reference genome. African ancestry variants from resources such as gnomAD were considered to enhance population\u2010specific relevance. Transcription factor binding sites were predicted using position weight matrices with an 80% relative score threshold to balance sensitivity and specificity. CpG island analysis was performed, including calculation of the observed\/expected (o\/e) ratio.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The 2501\u2009bp\n                      <jats:italic>Rac1<\/jats:italic>\n                      promoter is notably GC\u2010rich (57.34%) and contains 164 CpG sites with an o\/e ratio of 0.75, defining a canonical CpG island. Analysis revealed a complex regulatory landscape featuring binding motifs for the mineralocorticoid receptor (MR), suggesting a potential pathway for bypassing RAAS blockade and contributing to ACEI\/ARB resistance. Binding sites for hypoxia\u2010inducible factors, inflammatory mediators, and the erythroid\u2010specific factor GATA\u20101 were also identified. Spatial analysis showed nonrandom clustering of these elements, suggesting integrated response capabilities.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      The regulatory architecture of the\n                      <jats:italic>Rac1<\/jats:italic>\n                      promoter suggests a potential molecular basis for MR\u2010mediated resistance to ACEI\/ARB therapies while simultaneously providing a predictive link to enhanced malaria susceptibility through erythrocyte remodeling pathways. These findings offer a novel framework for understanding treatment\u2010resistant hypertension in malaria\u2010endemic regions and identify the\n                      <jats:italic>Rac1<\/jats:italic>\n                      promoter as a candidate nexus for developing dual\u2010disease therapeutic strategies tailored to high\u2010burden populations.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1155\/ijhy\/8287621","type":"journal-article","created":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T05:37:53Z","timestamp":1776836273000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The\n                    <i>Rac1<\/i>\n                    Promoter as a Molecular Nexus for Antihypertensive Therapy Resistance and Enhanced Malaria Susceptibility"],"prefix":"10.1155","volume":"2026","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9265-6397","authenticated-orcid":false,"given":"Selassie Louis","family":"Ameke","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3092-1348","authenticated-orcid":false,"given":"Kwadwo","family":"Fosu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucas","family":"Amenga-Etego","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1166-5756","authenticated-orcid":false,"given":"Kwabena Amofa Nketia","family":"Sarpong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1093-1517","authenticated-orcid":false,"given":"Samuel Kojo","family":"Kwofie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,21]]},"reference":[{"key":"e_1_2_9_1_2","doi-asserted-by":"publisher","DOI":"10.1186\/S12889-025-24647-3\/FIGURES\/12"},{"key":"e_1_2_9_2_2","doi-asserted-by":"publisher","DOI":"10.59298\/IDOSRJSR\/2024\/1.1.1219.100"},{"key":"e_1_2_9_3_2","doi-asserted-by":"publisher","DOI":"10.3390\/BIOMEDICINES12071582"},{"key":"e_1_2_9_4_2","doi-asserted-by":"publisher","DOI":"10.3390\/VETSCI12080777"},{"key":"e_1_2_9_5_2","doi-asserted-by":"publisher","DOI":"10.3390\/CELLS10071831"},{"key":"e_1_2_9_6_2","doi-asserted-by":"publisher","DOI":"10.1080\/21541248.2021.1878001"},{"key":"e_1_2_9_7_2","doi-asserted-by":"publisher","DOI":"10.3390\/CELLS13060472\/S1"},{"key":"e_1_2_9_8_2","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.115.06054\/-\/DC1"},{"key":"e_1_2_9_9_2","doi-asserted-by":"publisher","DOI":"10.3389\/FCVM.2021.680775\/BIBTEX"},{"key":"e_1_2_9_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-79052-0"},{"key":"e_1_2_9_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/S41467-020-17829-7"},{"key":"e_1_2_9_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/BIOINFORMATICS\/BTW821"},{"key":"e_1_2_9_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/J.IMMUNI.2025.07.022"},{"key":"e_1_2_9_14_2","doi-asserted-by":"publisher","DOI":"10.3389\/FGENE.2020.580580\/BIBTEX"},{"key":"e_1_2_9_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/S41594-023-01171-9"},{"key":"e_1_2_9_16_2","doi-asserted-by":"publisher","DOI":"10.1093\/NAR\/GKAB1113"},{"key":"e_1_2_9_17_2","doi-asserted-by":"publisher","DOI":"10.1186\/S12859-024-05995-0"},{"key":"e_1_2_9_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/S41587-024-02353-6"},{"key":"e_1_2_9_19_2","doi-asserted-by":"publisher","DOI":"10.3390\/APP15147925"},{"key":"e_1_2_9_20_2","doi-asserted-by":"publisher","DOI":"10.1186\/S13059-024-03300-Z\/FIGURES\/7"},{"key":"e_1_2_9_21_2","doi-asserted-by":"publisher","DOI":"10.3389\/FGENE.2024.1367731\/BIBTEX"}],"container-title":["International 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