Author:
Xiao Linxiao,Zou Xuelun,Liang Yan,Wang Yuxiang,Zeng Lang,Wu Jianhuang
Abstract
Aim: Since tissue inhibitors of matrix metalloproteinase 3 (TIMP-3) was reported to be a potential risk factor of atherosclerosis, aneurysm, hypertension, and post-ischaemic neuronal injury, it may also be a candidate risk factor of stress. Therefore, this study was designed to explore the causal role of TIMP-3 in the risk of ischaemic stroke (IS) and intracerebral haemorrhage (ICH), which are the two main causes of stress via this Mendelian Randomisation (MR) study.Methods: The summarised data of TIMP-3 level in circulation was acquired from the Cooperative Health Research in the Region of Augsburg public database and the outcome of IS and ICH was obtained from genome-wide association studies conducted by MEGASTROKE and the International Stroke Genetics Consortium, respectively. Five statistical methods including inverse-variance weighting, weighted-median analysis, MR-Egger regression, MR Pleiotropy RESidual Sum and Outlier test, and MR-Robust Adjusted Profile Score were applied to evaluate the causal role of TIMP-3 in the occurrence of IS and ICH. Inverse-variance weighting was applied for assessing causality. Furthermore, heterogeneity and pleiotropic tests were utilised to confirm the reliability of this study.Results: We found that TIMP-3 could be a positively causal relationship with the incidence of IS (OR = 1.026, 95% CI: 1.007–1.046, p = 0.0067), especially for the occurrence of small vessel stroke (SVS; OR = 1.045, 95% CI: 1.016–1.076, p = 0.0024). However, the causal effects of TIMP-3 on another IS subtype cardioembolic stroke (CES; OR = 1.049, 95% CI: 1.006–1.094, p = 0.024), large artery stroke (LAS; OR = 1.0027, 95% CI: 0.9755–1.0306, p = 0.849) and ICH (OR = 0.9900, 95% CI: 0.9403–1.0423, p = 0.701), as well as ICH subtypes were not observed after Bonferroni corrections (p = 0.00714).Conclusion: Our results revealed that high levels of circulating TIMP-3 causally increased the risk of developing IS and SVS, but not CES, LAS, ICH, and all ICH subtypes. Further investigation is required to elucidate the underlying mechanism.
Subject
Genetics (clinical),Genetics,Molecular Medicine
Cited by
1 articles.
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