Inflammatory Markers are Associated with Ischemic Stroke among Indigenous Africans: Evidence from the SIREN Study

Moustafa I Morsy; Fred Stephen Sarfo; Osahon Jeffery Asowata; Onoja Matthew Akpa; Joshua Odunayo Akinyemi; Albert Kwaku Akpalu; Olayinka J. Adebajo; Oladimeji Adebayo; Akinkunmi Paul Okekunle; Kazeem Akinwande; Paul Olowoyo; Ganiyu Amusa; Reginald Obiako; Oyedunni Arulogun; Daniel T. Lackland; Isah Suleiman Yahaya; Abiodun Moshood Adeoye; Olayemi Balogun; Elisabetta Caiazzo; Lucy McShane; Philip Oluleke Ibinaiye; Benedict NL Calys-Tagoe; Yaw Mensah; Adekunle Gregory Fakunle; Mayowa Ogunronbi; Osi Adeleye; Samuel Diala; Joseph  O. Yaria; Oladotun Olalusi; Akintomiwa Makanjuola

doi:10.1101/2025.08.10.25331295

Genetic & Genomic MedicinemedRxivAug 10, 2025

Preprint

Inflammatory Markers are Associated with Ischemic Stroke among Indigenous Africans: Evidence from the SIREN Study

Moustafa I Morsy iD, Fred Stephen Sarfo iD, Osahon Jeffery Asowata iD, Onoja Matthew Akpa iD, Joshua Odunayo Akinyemi iD, Albert Kwaku Akpalu iD, Olayinka J. Adebajo iD, Oladimeji Adebayo iD, Akinkunmi Paul Okekunle iD, Kazeem Akinwande iD, Paul Olowoyo iD, Ganiyu Amusa iD, Reginald Obiako iD, Oyedunni Arulogun iD, Daniel T. Lackland iD, Isah Suleiman Yahaya, Abiodun Moshood Adeoye iD, Olayemi Balogun iD, Elisabetta Caiazzo iD, Lucy McShane iD, Philip Oluleke Ibinaiye iD, Benedict NL Calys-Tagoe iD, Yaw Mensah, Adekunle Gregory Fakunle iD, Mayowa Ogunronbi iD, , Mayowa Ojo Owolabi iD

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Abstract

BackgroundInflammation might predispose to worse outcomes after an ischemic stroke. This has not been characterized among indigenous Africans. PurposeWe investigated the association between inflammatory biomarkers, stroke severity, and outcomes in Africans. MethodsThis is a retrospective analysis of a prospective study, including 90 participants with confirmed ischemic stroke selected from the Stroke Investigative Research & Educational Network (SIREN) cohort and 90 controls matched by age, sex, and ethnicity. Plasma concentrations of 368 protein biomarkers were analyzed (Olink(R) Explore 384 Inflammation panel) and compared between cases and controls. Further, we investigated the association between these proteins and stroke severity, lesion volume, and one-month post-stroke disability and fatality. ResultsDifferential protein expression analysis revealed 23 up-regulated and 14 down-regulated proteins in stroke cases versus controls. Among the up-regulated proteins, agouti-related protein (AgRP) and tumor necrosis factor receptor superfamily member 11A (TNFRSF11A) were the most significantly up-regulated, while interleukin-1 beta (IL-1{beta}) and integrin alpha-11 (ITGA11) were the most down-regulated proteins. Logistic regression analysis identified 72 proteins that were associated with stroke severity independent of age and sex. Among these, complement C1q subcomponent subunit A (C1qa) exhibited the strongest associations. Additionally, 14 proteins including C-C motif chemokine 23 (CCL23) were found to be associated with one-month post-stroke disability. ConclusionStroke disability and severity were associated with inflammation in an indigenous African population. The identified biomarkers might be useful for predicting stroke outcome or serve as therapeutic target. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=137 SRC="FIGDIR/small/25331295v1_ufig1.gif" ALT="Figure 1"> View larger version (38K): org.highwire.dtl.DTLVardef@a1c627org.highwire.dtl.DTLVardef@d86850org.highwire.dtl.DTLVardef@1a87f7forg.highwire.dtl.DTLVardef@14a99dc_HPS_FORMAT_FIGEXP M_FIG C_FIG