Association between Angiotensin Converting Enzyme Insertion/Deletion gene polymorphism with the risk of Hemorrhagic Stroke: A systematic review and Meta-Analysis of 53 studies.

BACKGROUND AND AIMS: Hemorrhagic stroke (HS) results in significant mortality and disability worldwide. Angiotensin Converting Enzyme (ACE) is responsible for blood pressure regulation and vascular homeostasis. Our objective was to conduct a comprehensive meta-analysis for ascertaining the association of ACE I/D polymorphism with HS since a number of studies depicted inconclusive evidence. METHODS: Literature search was performed till July 10, 2020 in PubMed, EMBASE, Cochrane, Chinese National Knowledge Information and Google Scholar databases with keywords: ('Angiotensin Converting Enzyme' OR 'ACE') AND ('Single Nucleotide polymorphisms' OR 'SNP') AND ('Hemorrhagic stroke or 'HS'). Pooled Odds Ratio (OR) and 95% Confidence Interval (CI) were determined for gene-disease association using either fixed (when I2 < 50%) or random effect (when I2 > 50%) models. Risk of bias in studies was assessed using funnel plots and sensitivity analyses. Statistical analysis was performed using STATA version 13.0 software. RESULTS: A total of 53 studies having 5186 HS and 7347 healthy control subjects were included in our meta-analysis. Pooled analyses showed that ACE I/D gene polymorphism had significant association with risk of HS in overall study population [(dominant model: OR = 1.29, 95% CI = 1.12-1.50 & recessive model: OR = 1.79, 95% CI = 1.46-2.20)]. Population subgroup analyses further revealed significant relationship of ACE I/D polymorphism with ICH in Asians (recessive: OR 1.97, 95% CI = 1.57-2.47) but not in Caucasians (recessive: OR 1.02, 95% CI = 0.76-1.36). CONCLUSION: This meta-analysis suggests that ACE I/D polymorphism may lead to risk of HS and can be a potential biomarker for HS susceptibility especially in Asian population.

Blood biomarkers for the diagnosis and differentiation of stroke: A systematic review and meta-analysis.

BACKGROUND: Correct diagnosis of stroke and its subtypes is pivotal in early stages for optimum treatment. AIMS: The aim of this systematic review and meta-analysis is to summarize the published evidence on the potential of blood biomarkers in the diagnosis and differentiation of stroke subtypes. METHODS: A literature search was conducted for papers published until 20 April 2020 in PubMed, EMBASE, Cochrane Library, TRIP, and Google Scholar databases to search for eligible studies investigating the role of blood biomarkers in diagnosing stroke. Quality assessment was done using modified Quality Assessment of Diagnostic Accuracy Studies questionnaire. Pooled standardized mean difference and 95% confidence intervals were calculated. Presence of heterogeneity among the included studies was investigated using the Cochran's Q statistic and I2 metric tests. If I2 was < 50% then a fixed-effect model was applied else a random-effect model was applied. Risk of bias was assessed using funnel plots and between-study heterogeneity was assessed using meta-regression and sensitivity analyses. Entire statistical analysis was conducted in STATA version 13.0. RESULTS: A total of 40 studies including patients with 5001 ischemic strokes, 756 intracerebral hemorrhage, 554 stroke mimics, and 1774 healthy control subjects analyzing 25 biomarkers (within 24 h after symptoms onset/after the event) were included in our meta-analysis; 67.5% of studies had moderate evidence of quality. Brain natriuretic peptide, matrix metalloproteinase-9, and D-dimer significantly differentiated ischemic stroke from intracerebral hemorrhage, stroke mimics, and health control subjects (p < 0.05). Glial fibrillary acidic protein successfully differentiated ischemic stroke from intracerebral hemorrhage (standardized mean difference -1.04; 95% confidence interval -1.46 to -0.63) within 6 h. No studies were found to conduct a meta-analysis of blood biomarkers differentiating transient ischemic attack from healthy controls and stroke mimics. CONCLUSION: This meta-analysis highlights the potential of brain natriuretic peptide, matrix metalloproteinase-9, D-dimer, and glial fibrillary acidic protein as diagnostic biomarkers for stroke within 24 h. Results of our meta-analysis might serve as a platform for conducting further targeted proteomics studies and phase-III clinical trials.PROSPERO Registration ID: CRD42019139659.

Association between matrix metalloproteinase family gene polymorphisms and risk of ischemic stroke: A systematic review and meta-analysis of 29 studies.

BACKGROUND: Ischemic stroke (IS) is a complex and devastating vascular disease that has become one of the leading causes of disability and mortality worldwide. Several studies have shown the association between matrix metalloproteinase (MMP) family gene polymorphisms and IS. However, the results have been indecisive. OBJECTIVE: To investigate the association between Matrix Metalloproteinase gene polymorphisms and risk of IS. METHODS: A literature search for eligible candidate gene studies published before, 28 June 2017, was conducted in the PubMed, EMBASE, Cochrane and Google Scholar databases. The following combinations of main keywords were used: ('Matrix Metalloproteinase' or 'MMP' or 'Stromelysin-1' or 'Gelatinase b') AND ('ischemic stroke' or 'IS') AND ('single nucleotide polymorphism' or 'gene polymorphism' or 'SNP'). Fixed or random effects models were used to estimate the Pooled Odds ratio (OR) and 95% confidence interval (CI). Statistical analysis was carried out by using STATA version 13.0 software. RESULTS: Total 29 studies were included in our meta-analysis. A significant association was observed for MMP-9 (-1562C/T) (OR 1.27; 95% CI 1.06 to 1.53; p value = 0.01) and MMP-12 (-1082 A/G) (OR 2.55; 95% CI 1.75 to 3.71; p value<0.001) gene polymorphisms and risk of IS. No significant association was found for any of the MMP-1(-1607 1G/2G), MMP-2 (-1306C/T) & (-735C/T) and MMP-3 (-1612 5A/6A) gene polymorphisms with the risk of IS. CONCLUSION: Our meta-analysis suggests that MMP-9 (-1562C/T) and MMP-12 (-1082 A/G) gene polymorphisms could be a risk factor for IS while MMP-1 (-1607 1G/2G), MMP-2 (-1306C/T) & (-735C/T) and MMP-3 (-1612 5A/6A) have no association with the risk of causing IS. However, large prospective studies with sufficient power are required to validate our findings.

Diagnostic accuracy of nucleic acid amplification based assays for tuberculous meningitis: A meta-analysis.

BACKGROUND: Numerous in-house and commercial nucleic acid amplification tests (NAAT) have been evaluated using variable reference standards for diagnosis of TBM but their diagnostic potential is still not very clear. METHODS: We conducted a meta-analysis to assess the diagnostic accuracy of different NAAT based assays for diagnosing TBM against 43 data sets of confirmed TBM (n = 1066) and 61 data sets of suspected TBM (n = 3721) as two reference standards. The summary estimate of the sensitivity and the specificity were obtained using the bivariate model. QUADAS-2 tool was used to perform the Quality assessment for bias and applicability. Publication bias was assessed with Deeks' funnel plot. RESULTS: Studies with confirmed TBM had better summary estimates as compared to studies with clinically suspected TBM irrespective of NAAT and index tests used. Among in-house assays, MPB as the gene target had best summary estimates in both confirmed [sensitivity:90%(83-95), specificity:97-%(87-99), DOR:247 (50-1221), AUC:99%(97-100), PLR:38.8-(6.6-133), NLR:0.11(0.05-0.18), I2 = 15%] and clinically suspected [sensitivity:69%(47-85), specificity:96%(90-98), DOR:62(16.8-232), AUC:94%(92-97), PLR:16.9(6.5-36.8), NLR:0.33(0.16-0.56), I2:15.3%] groups. GeneXpert revealed good diagnostic accuracy only in confirmed TBM group [sensitivity = 57%(38-74), specificity = 98%(89-100), DOR = 62(7-589), AUC = 87%(79-96), PLR = 33.2(3.8-128), NLR = 0.45(0.26-0.68), I2 = 0%]. CONCLUSIONS: This meta-analysis identified potential role of MPB gene among in-house assays and GeneXpert as commercial assay for diagnosing TBM.

Relationship between Factor V Leiden Gene Variant and Risk of Ischemic Stroke: A Case-Control Study.

BACKGROUND: Factor V Leiden is the most common genetic variation among the blood coagulation pathway which leads to prothrombotic state, therefore, is considered an important gene for understating the stroke mechanism. AIM: The aim of the present study is to determine the relationship between single nucleotide polymorphism at G1691A position of Factor V gene and risk of ischemic stroke (IS) in North Indian population. MATERIALS AND METHODS: In a retrospective case-control study, 250 patients with IS and 250 age- and gender-matched controls were enrolled in the period of October 2012 to September 2014 from in- and out-patient department of Neurology, All India Institute of Medical Sciences, New Delhi, India. Deoxyribonucleic acid for each case and control was isolated from peripheral blood using phenol-chloroform extraction method. Polymerase chain reaction-restriction fragment length polymorphism method was used to determine the polymorphism. Data were analyzed using STATA Software Version 13. RESULTS: The mean age of IS patient was 52.8 ± 12.5 years and in control group was 50.97 ± 12.7 years. Genotypic frequency distributions were in accordance with Hardy-Weinberg equilibrium in both cases and controls. As expected hypertension, diabetes, dyslipidemia, smoking, heavy alcohol intake, family history of stroke, and poor economic status were significantly associated with the risk of IS. Multivariate analysis revealed 5.17 times higher odds for developing the risk of large vessel subtype of IS in patients carrying Factor V Leiden G1691A gene variation as compared to control subjects (OR, 5.17; 95% CI, 1.32-20.3, P = 0.01). CONCLUSION: The present study suggests that Factor V Leiden G1691A polymorphism may be significantly associated with the risk of large vessel subtype of IS. Large sample size studies using prospective cohort designs are required to corroborate the present findings.