Urinary proteomic profiling revals molecular cues underlying higher hypertension susceptibility in blacks than whites

Abstract

Background and Objective: Compared with Whites, Blacks are more prone to hypertension and salt-sensitivity. The objective was to investigate whether sequenced urinary peptide fragments derived from proteins with a key role in cardiovascular or renal structure or function have different levels in sub-Saharan Blacks compared with Whites. Methods: This individual-participant meta-analysis included individuals enrolled in African-PREDICT (476 Blacks and 483 Whites), FLEMENGHO (720 Whites), PROVALID-Austria (467 Whites) and UPRIGHT-HTM (106 Nigerian Blacks and 61 Polish and Slovenian Whites). Urinary peptides were quantified by capillary electrophoresis combined with mass spectrometry. Results: Among 2313 participants (49.7% women), median age was 40.9 years. Of 513 urinary peptides with 70% prevalence, 300 had Bonferroni-corrected significantly different levels among Black and White South Africans sharing the same environment. Analyses contrasting 582 Blacks vs 1731 Whites, sub-Saharan Blacks (582) vs European Whites (1248) replicated the findings. Combining these results with information from public databases, we identified COL4A1, COL4A2, CD99, FAT1, FGA, FXYD2, MGP, MYOCD, PCDH7, PROC, and UMOD as most likely candidates underlying the different susceptibility to hypertension and salt sensitivity between Blacks and Whites. The most relevant enriched pathways were related to hemostasis, platelet activity, collagens and biology of the extra-cellular matrix, and protein digestion and absorption. Disease Ontology terms comprised small-vessel disease and coronary and macrovascular atherosclerotic disease. Conclusions: MGP and MYOCD being involved in cardiovascular function, FGA in clot formation, FYXD2 and UMOD in salt homeostasis, and COL4A1 and COL4A2 as major component of the glomerular basement membrane are proteins deserving further exploration in molecular and human studies as potential targets for intervention to reduce the excess hypertension risk and associated complications in Blacks.