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This cross\u2010sectional analysis of a multi\u2010ethnic cohort aimed to search for proteins potentially involved in the susceptibility to salt sensitivity, hypertension, and hypertension\u2010related complications. The study included individuals enrolled in African Prospective Study on the Early Detection and Identification of Cardiovascular Disease and Hypertension (African\u2010PREDICT), Flemish Study of the Environment, Genes and Health Outcomes (FLEMENGHO), Prospective Cohort Study in Patients with Type 2 Diabetes Mellitus for Validation of Biomarkers (PROVALID)\u2010Austria, and Urinary Proteomics Combined with Home Blood Pressure Telemonitoring for Health Care Reform Trial (UPRIGHT\u2010HTM). Sequenced urinary peptides detectable in 70% of participants allowed the identification of parental proteins and were compared between Blacks and Whites. Of 513 urinary peptides, 300 had significantly different levels among healthy Black (<jats:italic>n<\/jats:italic>\u00a0=\u00a0476) and White (<jats:italic>n<\/jats:italic>\u00a0=\u00a0483) South Africans sharing the same environment. Analyses contrasting 582 Blacks versus 1731 Whites, and Sub\u2010Saharan Blacks versus European Whites replicated the findings. COL4A1, COL4A2, FGA, PROC, MGP, MYOCD, FYXD2, and UMOD were identified as the most likely candidates underlying the racially different susceptibility to salt sensitivity, hypertension, and related complications. Enriched pathways included hemostasis, platelet activity, collagens, biology of the extracellular matrix, and protein digestion and absorption. Our study suggests that MGP and MYOCD being involved in cardiovascular function, FGA and PROC in coagulation, FYXD2 and UMOD in salt homeostasis, and COL4A1 and COL4A2 as major components of the glomerular basement membrane are among the many proteins potentially incriminated in the higher susceptibility of Blacks compared to Whites to salt sensitivity, hypertension, and its complication. Nevertheless, these eight proteins and their associated pathways deserve further exploration in molecular and human studies as potential targets for intervention to reduce the excess risk of hypertension and cardiovascular complications in Blacks versus Whites.<\/jats:p>","DOI":"10.1002\/pmic.202400207","type":"journal-article","created":{"date-parts":[[2024,11,24]],"date-time":"2024-11-24T08:25:28Z","timestamp":1732436728000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Urinary Proteomics and Systems Biology Link Eight Proteins to the Higher Risk of Hypertension and Related Complications in Blacks Versus Whites"],"prefix":"10.1002","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1395-7050","authenticated-orcid":false,"given":"De\u2010Wei","family":"An","sequence":"first","affiliation":[{"name":"Department of Cardiovascular Medicine Shanghai Key Laboratory of Hypertension Shanghai Institute of Hypertension State Key Laboratory of Medical Genomics National Research Center for Translational Medicine Ruijin Hospital Shanghai Jiaotong University School of Medicine  Shanghai China"},{"name":"Non\u2010Profit Research Association Alliance for the Promotion of Preventive Medicine  Mechelen Belgium"},{"name":"Research Unit Environment and Health KU Leuven Department of Public Health and Primary Care University of Leuven  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7893-3642","authenticated-orcid":false,"given":"Dries S.","family":"Martens","sequence":"additional","affiliation":[{"name":"Center for Environmental Sciences Hasselt University  Diepenbeek Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6203-3965","authenticated-orcid":false,"given":"Gontse G.","family":"Mokwatsi","sequence":"additional","affiliation":[{"name":"Hypertension in Africa Research Team (HART) SAMRC Extramural Unit for Hypertension and Cardiovascular Disease, Faculty of Health Sciences North\u2010West University  Potchefstroom South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8255-3770","authenticated-orcid":false,"given":"Yu\u2010Ling","family":"Yu","sequence":"additional","affiliation":[{"name":"Non\u2010Profit Research Association Alliance for the Promotion of Preventive Medicine  Mechelen Belgium"},{"name":"Research Unit Environment and Health KU Leuven Department of Public Health and Primary Care University of Leuven  Leuven Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4727-1647","authenticated-orcid":false,"given":"Babangida S.","family":"Chori","sequence":"additional","affiliation":[{"name":"Center for Environmental Sciences Hasselt University  Diepenbeek Belgium"},{"name":"Circulatory Health Research Laboratory College of Health Sciences University of Abuja  Abuja Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8917-2412","authenticated-orcid":false,"given":"Agnieszka","family":"Latosinska","sequence":"additional","affiliation":[{"name":"Mosaiques Diagnostiques GmbH  Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4661-6727","authenticated-orcid":false,"given":"Godsent","family":"Isiguzo","sequence":"additional","affiliation":[{"name":"Cardiology Unit Department of Medicine Alex Ekwueme Federal University Teaching Hospital &amp; 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