Genetically Determined Plasma Hepatocyte Growth Factor Levels Are Associated With the Risk and Prognosis of Ischemic Stroke

Qingyun Xu; Daoxia Guo; Mengyao Shi; Yinan Wang; Pinni Yang; Yiming Jia; Lulu Sun; Yi Liu; Xinyue Chang; Yu He; Li Hui; Yonghong Zhang; Zhengbao Zhu

doi:10.1161/STROKEAHA.123.045430

Genetically Determined Plasma Hepatocyte Growth Factor Levels Are Associated With the Risk and Prognosis of Ischemic Stroke

Stroke. 2024 Apr 4. doi: 10.1161/STROKEAHA.123.045430. Online ahead of print.

Authors

Qingyun Xu^#¹, Daoxia Guo^#², Mengyao Shi¹, Yinan Wang¹, Pinni Yang¹, Yiming Jia¹, Lulu Sun¹, Yi Liu¹, Xinyue Chang¹, Yu He¹, Li Hui³, Yonghong Zhang¹, Zhengbao Zhu¹

Affiliations

¹ Department of Epidemiology, School of Public Health, Jiangsu Key Laboratory of Preventive and Translational Medicine for Major Chronic Non-communicable Diseases, MOE Key Laboratory of Geriatric Diseases and Immunology, Suzhou Medical College of Soochow University, China. (Q.X., M.S., Y.W., P.Y., Y.J., L.S., Y.L., X.C., Y.H., Y.Z., Z.Z.).
² School of Nursing, Suzhou Medical College of Soochow University, China. (D.G.).
³ Research Center of Biological Psychiatry, The Affiliated Guangji Hospital of Soochow University, Suzhou, China (L.H.).

^# Contributed equally.

PMID: 38572663
DOI: 10.1161/STROKEAHA.123.045430

Abstract

Background: Observational studies suggest that hepatocyte growth factor (HGF) is associated with the risk and prognosis of ischemic stroke, but the causality of these associations remains unclear. Therefore, we conducted Mendelian randomization (MR) analyses to explore the associations of genetically determined plasma HGF levels with the risk and prognosis of ischemic stroke.

Methods: A total of 13 single-nucleotide polymorphisms associated with plasma HGF were selected as genetic instruments based on the data from a genome-wide association study with 21 758 European participants. Summary data about the risk of ischemic stroke were obtained from the MEGASTROKE (Multiancestry Genome-Wide Association Study of Stroke) Consortium with 34 217 ischemic stroke cases and 406 111 controls of European ancestry, and summary data about the prognosis of ischemic stroke were obtained from the GISCOME study (Genetics of Ischaemic Stroke Functional Outcome) with 6165 European patients with ischemic stroke. We conducted an inverse-variance weighted Mendelian randomization analysis followed by a series of sensitivity analyses to evaluate the associations of genetically determined plasma HGF with the risk and prognosis of ischemic stroke.

Results: The primary analyses showed that genetically determined high HGF was associated with an increased risk of ischemic stroke (odds ratio per SD increase, 1.11 [95% CI, 1.04-1.19]; P=1.10×10^-3) and poor prognosis of ischemic stroke (odds ratio per SD increase, 2.43 [95% CI, 1.76-3.52]; P=6.35×10^-8). In the secondary analysis, genetically determined plasma HGF was associated with a high risk of large atherosclerotic stroke (odds ratio per SD increase, 1.39 [95% CI, 1.18-1.63]; P=5.08×10^-5) but not small vessel stroke and cardioembolic stroke. Mendelian randomization-Egger regression showed no directional pleiotropy for all associations, and the sensitivity analyses with different Mendelian randomization methods further confirmed these findings.

Conclusions: We found positive associations of genetically determined plasma HGF with the risk and prognosis of ischemic stroke, suggesting that HGF might be implicated in the occurrence and development of ischemic stroke.

Keywords: cardiovascular diseases; hepatocyte growth factor; ischemic stroke; prevalence; prognosis.