Three Proteins Linked to Stroke Recovery in Genetic Study
Researchers identified three inflammation-related proteins that genetically influence how well stroke patients recover, offering potential new drug targets. The findings could reshape how doctors predict outcomes and develop treatments for the 795,000 Americans who suffer strokes annually, a market opportunity for diagnostics and therapeutics companies.
Originaltitel: Genetically Determined Levels of Inflammation-Related Proteins and Functional Outcome After Ischemic Stroke: A Mendelian Randomization Study
Directionally concordant results were observed for three proteins in the secondary MR analysis: HGF (OR, 0.14 [0.06-0.37],FDR<0.001),CASP-8 (OR, 0.56 [0.33-0.94],P=0.028), and S100A12 (OR, 3.02 [1.32-6.90],FDR=0.045)(Figure 2B; details provided in Supplementary Tables 910111213).No significant or suggestive associations were observed for any of the remaining proteins.Our MR analyses indicate that S100A12 and MCP-3 exert a causal detrimental influence on ischemic stroke outcomes, aligning with clinical observations that elevated acute-phase levels are associated with poor outcomes. 2Importantly, MR reflects a lifelong genetic predisposition to constitutive protein exposure rather than transient post-injury responses.This distinction is Figure 1.Study design and workflow for MR analyzing the causal relation between inflammatory proteins (UK Biobank Pharma Proteomics Project) and func- tional outcome after ischemic stroke (GISCOME).Genetic instruments were filtered and adjusted for collider bias (GIGASTROKE).Four proteins were ineligible for downstream analysis (IL-6, STAMBP, 4E-BP1, and OSM because of having less than three SNPs and r <0.005).For the 10 remaining proteins, analyses were performed using both NIHSS-adjusted and unadjusted data, followed by comprehensive sensitivity analyses.GISCOME, Genetics of Ischemic Stroke Functional Outcome;