The ACTB Variants and Alcohol Drinking Confer Joint Effect to Ischemic Stroke in Chinese Han Population

Yang, Song; Zhao, Yongqiang; Chen, Xiaotian; Lu, Xiangfeng; Chen, Yanchun; Zhao, Xianxian; Zhu, Lijun; Fang, Zhengmei; Zhao, Hailong; Yao, Yingshui; Liu, Chunlan; Shen, Chong

doi:10.5551/jat.49536

Cited by 15 publications

(13 citation statements)

References 25 publications

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“…Moreover, the expression level of several stroke-associated inflammatory genes, such as VCAM-1, SMAHD-1, and DDAH1, were significantly upregulated in COVID-19 positive patients, indicating that the inflammatory response may play potential roles in mediating COVID-19-associated stroke. As mentioned above, the expression levels of HMOX1, LTC4S, and ACTB seem to have negative correlation relationships with the risk of cerebral ischemia ( Freiberg et al, 2010 ; Nitti et al, 2018 ; Cui et al, 2020 ; Yang et al, 2020 ), the significant downregulation of HMOX1, LTC4S, and ACTB in PBMC samples from COVID-19 positive patients may indicate possible molecular mechanisms between COVID-19 and stroke. However, further clinical and functional studies using COVID-19 patient samples or animal models are highly needed to investigate direct viral infection effects and indirect inflammatory effects on human brains by SARS-CoV-2.…”

Section: Resultsmentioning

confidence: 79%

The Epidemiological and Mechanistic Understanding of the Neurological Manifestations of COVID-19: A Comprehensive Meta-Analysis and a Network Medicine Observation

et al. 2021

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The clinical characteristics and biological effects on the nervous system of infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remain poorly understood. The aim of this study is to advance epidemiological and mechanistic understanding of the neurological manifestations of coronavirus disease 2019 (COVID-19) using stroke as a case study. In this study, we performed a meta-analysis of clinical studies reporting stroke history, intensive inflammatory response, and procoagulant state C-reactive protein (CRP), Procalcitonin (PCT), and coagulation indicator (D-dimer) in patients with COVID-19. Via network-based analysis of SARS-CoV-2 host genes and stroke-associated genes in the human protein-protein interactome, we inspected the underlying inflammatory mechanisms between COVID-19 and stroke. Finally, we further verified the network-based findings using three RNA-sequencing datasets generated from SARS-CoV-2 infected populations. We found that the overall pooled prevalence of stroke history was 2.98% (95% CI, 1.89–4.68; I2=69.2%) in the COVID-19 population. Notably, the severe group had a higher prevalence of stroke (6.06%; 95% CI 3.80–9.52; I2 = 42.6%) compare to the non-severe group (1.1%, 95% CI 0.72–1.71; I2 = 0.0%). There were increased levels of CRP, PCT, and D-dimer in severe illness, and the pooled mean difference was 40.7 mg/L (95% CI, 24.3–57.1), 0.07 μg/L (95% CI, 0.04–0.10) and 0.63 mg/L (95% CI, 0.28–0.97), respectively. Vascular cell adhesion molecule 1 (VCAM-1), one of the leukocyte adhesion molecules, is suspected to play a vital role of SARS-CoV-2 mediated inflammatory responses. RNA-sequencing data analyses of the SARS-CoV-2 infected patients further revealed the relative importance of inflammatory responses in COVID-19-associated neurological manifestations. In summary, we identified an elevated vulnerability of those with a history of stroke to severe COVID-19 underlying inflammatory responses (i.e., VCAM-1) and procoagulant pathways, suggesting monotonic relationships, thus implicating causality.

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Section: Resultsmentioning

confidence: 79%

The Epidemiological and Mechanistic Understanding of the Neurological Manifestations of COVID-19: A Comprehensive Meta-Analysis and a Network Medicine Observation

et al. 2021

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“…However, some studies showed that ACTB might not be an optimal reference gene for the normalization of gene expression in whole blood under the pressure of certain diseases such as stroke, which induces alterations in the cellular composition of the peripheral immune system (Stamova et al, 2009;Sieber et al, 2010). Additionally, our previous studies have shown that ACTB variants may confer genetic susceptibility to stroke and diabetic kidney disease (DKD) in a Chinese Han population (Li et al, 2019;Yang et al, 2020). However, little is yet known about the epigenetic impact of ACTB on the initiation and progress of stroke.…”

Section: Discussionmentioning

confidence: 99%

“…Moustafa-Bayoumi et al (2007) suggested that elevated actin polymerization and stress fiber formation would generate mechanical force to trigger the hypertrophic signaling pathway, subsequently resulting in vascular remodeling and hypertension that can reduce blood flow in brain and alter the mechanics and function of cerebral blood vessels, and ultimately increase the risk of stroke (Legrand et al, 1993;Ibrahim et al, 2006). Our previous study showed that ACTB polymorphisms may contribute to the genetic susceptibility to stroke (Yang et al, 2020), although the mechanism of ACTB polymorphisms to stroke remains unclear. Taken together, all the identified stroke-related genetic factors account for only 5-10% of the risk of stroke (Bevan et al, 2012;Malik and Dichgans, 2018).…”

Section: Introductionmentioning

confidence: 99%

ACTB Methylation in Blood as a Potential Marker for the Pre-clinical Detection of Stroke: A Prospective Nested Case-Control Study

Liu

Yin

et al. 2021

Front. Neurosci.

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BackgroundStroke is the second leading cause of death worldwide. If risk of stroke could be evaluated early or even at a preclinical stage, the mortality rate could be reduced dramatically. However, the identified genetic factors only account for 5–10% of the risk of stroke. Studies on the risk factors of stroke are urgently needed. We investigated the correlation between blood-based β-actin (ACTB) methylation and the risk of stroke in a prospective nested case-control study.MethodsThe methylation level of ACTB was quantitatively determined by mass spectrometry in 139 stroke cases who developed stroke within 2 years after recruitment and 147 age- and sex-matched controls who remained stroke-free in a median follow-up of 2.71 years.ResultsWe observed a highly significant correlation between hypomethylation of one CpG site of ACTB and increased risk of stroke in an onset-time-dependent manner (for onset time ≤ 1.5 years: odds ratio (OR) per + 10% methylation = 0.76, P = 0.001; for onset time ≤ 1.32 years: OR per + 10% methylation = 0.59, P = 7.82 × 10–7; for onset time ≤ 1 year: OR per + 10% methylation = 0.43, P = 3.00 × 10–6), and the increased cumulative incidence of stroke (log-rank P = 3.13 × 10–7). Neighboring CpG sites showed an inverse correlation with age and drinking status in controls (P < 0.05) but not in stroke cases.ConclusionWe firstly reported the blood-based ACTB methylation as a marker for the risk evaluation and preclinical detection of stroke, which can be further modified by age and drinking.

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“…Hence, the current state of cardiovascular and cerebrovascular diseases can be judged by observing the factors. On the other hand, since personal health data such as smoking [ 19 ], alcoholism [ 20 ], history of hypertension [ 21 ] and history of hyperlipidaemia have strong correlations with stroke [ 22 ], it is necessary to combine personal health data to infer the possibility and probability of stroke attack. Table 3 lists the predictors related to stroke used in this article.…”

Section: Methodsmentioning

confidence: 99%

The Probability of Ischaemic Stroke Prediction with a Multi-Neural-Network Model

Liu

Yin

Yang

2020

Sensors

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As is known, cerebral stroke has become one of the main diseases endangering people’s health; ischaemic strokes accounts for approximately 85% of cerebral strokes. According to research, early prediction and prevention can effectively reduce the incidence rate of the disease. However, it is difficult to predict the ischaemic stroke because the data related to the disease are multi-modal. To achieve high accuracy of prediction and combine the stroke risk predictors obtained by previous researchers, a method for predicting the probability of stroke occurrence based on a multi-model fusion convolutional neural network structure is proposed. In such a way, the accuracy of ischaemic stroke prediction is improved by processing multi-modal data through multiple end-to-end neural networks. In this method, the feature extraction of structured data (age, gender, history of hypertension, etc.) and streaming data (heart rate, blood pressure, etc.) based on a convolutional neural network is first realized. A neural network model for feature fusion is then constructed to realize the feature fusion of structured data and streaming data. Finally, a predictive model for predicting the probability of stroke is obtained by training. As shown in the experimental results, the accuracy of ischaemic stroke prediction reached 98.53%. Such a high prediction accuracy will be helpful for preventing the occurrence of stroke.

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The ACTB Variants and Alcohol Drinking Confer Joint Effect to Ischemic Stroke in Chinese Han Population

Cited by 15 publications

References 25 publications

The Epidemiological and Mechanistic Understanding of the Neurological Manifestations of COVID-19: A Comprehensive Meta-Analysis and a Network Medicine Observation

The Epidemiological and Mechanistic Understanding of the Neurological Manifestations of COVID-19: A Comprehensive Meta-Analysis and a Network Medicine Observation

ACTB Methylation in Blood as a Potential Marker for the Pre-clinical Detection of Stroke: A Prospective Nested Case-Control Study

The Probability of Ischaemic Stroke Prediction with a Multi-Neural-Network Model

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