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

Mengmeng Wang; Zhizhong Zhang; Dandan Liu; Ville Karhunen; Marios K Georgakis; Yi Ren; Dan Ye; Dipender Gill; Meng Liu

doi:10.1016/j.jstrokecerebrovasdis.2023.107136

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

J Stroke Cerebrovasc Dis. 2023 Jun;32(6):107136. doi: 10.1016/j.jstrokecerebrovasdis.2023.107136. Epub 2023 Apr 15.

Authors

Mengmeng Wang¹, Zhizhong Zhang², Dandan Liu³, Ville Karhunen⁴, Marios K Georgakis⁵, Yi Ren⁶, Dan Ye⁶, Dipender Gill⁷, Meng Liu⁶

Affiliations

¹ Department of Neurology, The Third Affiliated Hospital of Soochow University, Changzhou, China. Electronic address: wangmeng_neuro@163.com.
² Department of Neurology, Jinling Hospital, Medical School of Nanjing University, Nanjing, China.
³ Department of Integrated Traditional Chinese and Western Medicine, The Third Affiliated Hospital of Soochow University, Changzhou, China.
⁴ Research Unit of Mathematical Sciences, University of Oulu, Oulu, Finland; Center for Life Course Health Research, Faculty of Medicine, University of Oulu, Oulu, Finland.
⁵ Institute for Stroke and Dementia Research (ISD), University Hospital, Ludwig-Maximilians-University (LMU), Munich, Germany; Center for Genomic Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
⁶ Department of Neurology, The Third Affiliated Hospital of Soochow University, Changzhou, China.
⁷ Department of Epidemiology and Biostatistics, School of Public Health, St Mary's Hospital, Imperial College London, London, United Kingdom.

PMID: 37068323
DOI: 10.1016/j.jstrokecerebrovasdis.2023.107136

Abstract

Objectives: 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.

Methods: 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).

Results: 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).

Conclusions: 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.

Keywords: Mendelian randomization analysis; Prognosis; Soluble adhesion molecules; Stroke.

MeSH terms

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
Selectins
Stroke* / diagnosis
Stroke* / genetics
Stroke* / therapy
Vascular Cell Adhesion Molecule-1 / genetics

Substances

Vascular Cell Adhesion Molecule-1
Cell Adhesion Molecules
Intercellular Adhesion Molecule-1
Selectins