Association between Factor V Gene Polymorphism and Risk of Ischemic Stroke: An Updated Meta-Analysis

Alhazzani, Adel; Kumar, Amit; Selim, Magdy

doi:10.1016/j.jstrokecerebrovasdis.2017.12.006

Cited by 15 publications

(8 citation statements)

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“…FA5 is the most prevalent genetic variation that leads to prothrombotic state; this gene is therefore considered important for understanding the mechanisms of stroke (23). Another previous study revealed that FA5 polymorphisms confer an increased risk of ischemic stroke in younger adults (24). Furthermore, Bhattacharjee et al reported that the FA5 activator might be associated with Alzheimer's disease; the FA5 activator destabilized Aβ aggregates, which may be useful for disease prevention in the future (25).…”

Section: Discussionmentioning

confidence: 98%

Proteomic Analysis of Preoperative CSF Reveals Risk Biomarkers of Postoperative Delirium

et al. 2020

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Objective: To analyze the proteome of preoperative cerebrospinal fluid (CSF) in older orthopedic patients with or without postoperative delirium (POD) using untargeted proteomics.Methods: A prospective cohort study was conducted. Eighty hip fracture patients aged ≥65 years were recruited. After successful spinal anesthesia, CSF was collected. The patients were divided into POD and No-POD groups based on the Confusion Assessment Method, and patients with POD were graded using the Memorial Delirium Assessment Scale (MDAS). Thirty No-POD patients were matched to 10 POD patients by age (±2 years) and Mini-Mental State Examination score (±2 scores). Label-free proteomic analysis was performed using a liquid chromatography coupled to mass spectrometry (LC-MS) workflow. Validation was performed using mass-spectrometry-based parallel reaction monitoring (PRM) for the 30 No-POD and 10 POD patients, as well as for an additional 5 POD patients. Bioinformatics were used to investigate possible relevant pathological mechanisms.Results: The incidence of POD in older orthopedic patients was 18.8% in our cohort of 80 patients. Proteomics results revealed 63 dysregulated CSF proteins, and PRM analysis validated these results. The preoperative CSF levels of both V-set and transmembrane domain-containing protein 2B (VSTM2B) and coagulation factor V (FA5) were positively correlated with MDAS scores on postoperative day 1 (r > 0.8, p < 0.05). Bioinformatic analysis revealed that several nervous-system-related pathways are relevant to POD development. Conclusion:We identified and validated several novel CSF proteins that are dysregulated in POD, and revealed several pathways that are relevant to POD development. Our results not only provide risk biomarkers for POD, but also give clues for further investigations into the pathological mechanisms of delirium. Clinical trial registration: This study was registered in the Chinese Clinical Trial Registry (ChiCTR1900021533).

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Section: Discussionmentioning

confidence: 98%

Proteomic Analysis of Preoperative CSF Reveals Risk Biomarkers of Postoperative Delirium

et al. 2020

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“…Inherited thrombophilia is a group of disorders including factor V Leiden or Prothrombin mutation, deficiency of Antithrombin, protein C and protein S, and hyperhomocysteinemia caused by mutations in methylenetetrahydrofolate reductase ( 23 , 24 ). Studies have shown an inconsistent or weak association between inherited thrombophilia and ischemic stroke ( 23 – 25 ), although a moderately stronger risk was reported in a subgroup of younger patients ( 25 , 26 ). Our study focused on ESUS with embolism as a likely cause of stroke and we did not include patients with malignancy or inherited thrombophilia, in which a hypercoagulable state is a potential mechanism.…”

Section: Discussionmentioning

confidence: 99%

Potential Embolic Sources Differ in Patients With Embolic Stroke of Undetermined Source According to Age: A 15-Year Study

et al. 2022

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IntroductionUnderstanding the potential embolic source in young patients with ESUS may improve the diagnosis and treatment of such patients.HypothesisPotential embolic sources (PES) differ in young vs. older patients with ESUS, and, therefore, not all patients with ESUS have the same risk profile for stroke recurrence.MethodsYoung patients (age 18-49) with ESUS, who were admitted to our stroke center from 2006 to 2019, were identified retrospectively and matched with next consecutive older patients (age 50–99) with ESUS by admission date. PES were categorized as atrial cardiopathy, AFib diagnosed during follow-up, left ventricular disease (LVD), cardiac valvular disease (CVD), PFO or atrial septal aneurysm (ASA), and arterial disease. Patients, who had cancer or thrombophilia, were excluded. The type and number of PES and stroke recurrence rates were determined and compared between young and older patients.ResultsIn young patients (55.3% women, median age 39 years), the most common PES was PFO/ASA, and the rate of other PES was low (2–7%). Half of the young patients (54.1%) had a single PES, only 10% had multiple PES, and 35.3% of young patients did not have any PES identified. In older patients (41.7% women, median age 74 years), the 3 most common PES were atrial cardiopathy (38.1%), LVD (35.7%), and arterial disease (23.8%). Nearly half of older patients (42.9%) had multiple PES. The rate of stroke recurrence tended to be lower in young patients as compared to older patients (4.9 vs. 11.4%, p = 0.29). During a median follow-up of 3 years, only 3 young patients (4.9%) had a recurrent stroke, and two of them had unclosed PFO. There were no recurrent strokes among young patients with no PES identified.ConclusionsIt was noted that PES differ in patients with ESUS according to age and differences in recurrence. PFO is the only common PES in young patients with ESUS. Future studies prospectively evaluating PES in both age groups are needed.

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“…Emerging evidences from published meta-analysis and GWAS studies suggests that several genetic variants (MTHFR, MMP9, PDE4D, CYP4A11, ALOX5P, NOTCH, NINJ2, FGB, eNOS, PITX2, ZFHX3, HDAC9, ABO, etc) have been identified, even though the extent of the effect of each variant is regarded as inter-varying within different populations including Asian, Caucasian, African. [1,1,7,14,[35][36][37][38][39][39][40][41][42][43][44] The findings, however, are often unclear and hard to interpret. Genetic association studies in diverse stroke populations negate matters of the restricted patient population by the a priori choice of a functionally relevant gene and its relation with a specific phenotype.…”

Section: Discussionmentioning

confidence: 99%

Potential Key Genes Associated with Stroke types and its subtypes: A Computational Approach

Das

Kumar

2021

Preprint

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To investigate prospective key genes and pathways associated with the pathogenesis and prognosis of stroke types along with subtypes. Human genes using genome assembly build 38 patch release 13 with known gene symbols through NCBI gene database (https://www.ncbi.nlm.nih.gov/gene) were fetched. PubMed advanced queries were constructed using stroke-related keywords and associations were calculated using Normalized pointwise mutual information (nPMI) between each gene symbol and queries. Genes related with stroke risk within their types and subtypes were investigated in order to discover genetic markers to predict individuals who are at the risk of developing stroke with their subtypes. A total of 2,785 (9.4%) genes were found to be linked to the risk of stroke. Based on stroke types, 1,287 (46.2%) and 376 (13.5%) genes were found to be related with IS and HS respectively. Further stratification of IS based on TOAST classification, 86 (6.6%) genes were confined to Large artery atherosclerosis; 131 (10.1%) and 130 (10%) genes were related with the risk of small vessel disease and Cardioembolism subtypes of IS. Besides, a prognostic panel of 9 genes signature consisting of CYP4A11, ALOX5P, NOTCH, NINJ2, FGB, MTHFR, PDE4D, HDAC9, and ZHFX3 can be treated as a diagnostic marker to predict individuals who are at the risk of developing stroke with their subtypes.

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Association between Factor V Gene Polymorphism and Risk of Ischemic Stroke: An Updated Meta-Analysis

Cited by 15 publications

References 49 publications

Proteomic Analysis of Preoperative CSF Reveals Risk Biomarkers of Postoperative Delirium

Proteomic Analysis of Preoperative CSF Reveals Risk Biomarkers of Postoperative Delirium

Potential Embolic Sources Differ in Patients With Embolic Stroke of Undetermined Source According to Age: A 15-Year Study

Potential Key Genes Associated with Stroke types and its subtypes: A Computational Approach

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