Soluble adhesion molecules and functional outcome after ischemic stroke: A Mendelian randomization study

• Published in: Journal of stroke and cerebrovascular diseases 2023-06, Vol.32 (6), p.107136-107136, Article 107136
• Main Authors: Wang, Mengmeng, Zhang, Zhizhong, Liu, Dandan, Karhunen, Ville, Georgakis, Marios K., Ren, Yi, Ye, Dan, Gill, Dipender, Liu, Meng
• Format: Article
• Language: English
• Subjects: Brain Ischemia - diagnosis; Brain Ischemia - genetics; Brain Ischemia - therapy; Cell Adhesion Molecules - genetics; Humans; Intercellular Adhesion Molecule-1 - genetics; Ischemic Stroke - diagnosis; Ischemic Stroke - genetics; Ischemic Stroke - therapy; Mendelian Randomization Analysis; Prognosis; Selectins; Soluble adhesion molecules; Stroke; Stroke - diagnosis; Stroke - genetics; Stroke - therapy; Vascular Cell Adhesion Molecule-1 - genetics
• ISSN: 1052-3057; 1532-8511
• DOI: 10.1016/j.jstrokecerebrovasdis.2023.107136

We employed Mendelian randomization to determine whether genetically predicted circulating levels of endothelial-derived adhesion molecules (soluble intercellular adhesion molecule-1 [sICAM-1]), soluble vascular-leukocyte adhesion molecule-1 [sVCAM-1], and soluble-endothelial-leukocyte adhesion molecule [sE-selectin]) were associated with functional outcome after ischemic stroke. Independent genetic variants robustly associated with soluble adhesion molecules, located at or close to the coding gene (cis), were used as genetic instruments. The functional outcome was evaluated using the 3-month modified Rankin Scale (mRS) score after ischemic stroke. A poor functional outcome was defined as mRS ≥ 3 at 3 months. We extracted summary data for functional outcome after ischemic stroke from the Genetics of Ischaemic Stroke Functional Outcome network (n = 6,021). Genetically elevated sICAM-1 (OR 1.28, 95% CI 1.05-1.56) and sE-selectin (OR 2.69, 95% CI 1.23-5.86) levels were related with poor post-stroke outcome. However, we found no evidence that genetically elevated sVCAM-1 were associated with post-stroke outcome (OR 1.36, 95% CI 0.39-4.66). We found that genetically elevated higher sICAM-1 and sE-selectin levels are associated with poor post-stroke outcome. Further studies are warranted to evaluate the potential of ICAM-1 and E-selectin to be drug targets for post-stroke recovery.