scholarly journals Long non-coding RNA H19 expression and functional polymorphism rs217727 are linked to increased ischemic stroke risk

BMC Neurology ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Mohadese Rezaei ◽  
Mohammad Javad Mokhtari ◽  
Mahnaz Bayat ◽  
Anahid Safari ◽  
Mehdi Dianatpuor ◽  
...  

Abstract Background Efforts to identify potential biomarkers for the diagnosis of ischemic stroke (IS) are valuable. The H19 gene plays a functional role in increasing the prevalence of IS risk factors. We evaluated the correlation between H19 rs217727 polymorphism and the expression level of H19 lncRNA with susceptibility to IS among the Iranian population. Methods Blood samples were collected from IS patients (n = 114) and controls (n = 114). We concentrated on the expression pattern of H19 at different time points (i.e., 0–24, 24–48, and 48–72 h after stroke). The tetra-amplification refractory mutation system-polymerase chain reaction (T-ARMS-PCR) method was applied for DNA genotyping. We used the quantitative real-time PCR to evaluate H19 expression levels. We used the receiver operating characteristic (ROC) curve to evaluate the diagnosis and prognosis of IS. Results The rs217727polymorphism of H19 was related with IS susceptibility in the co-dominant (OR = 2.92, 95% CI = 0.91–10.92, P = 0.04) and recessive models (OR = 2.80, 95% CI = 0.96–8.15, P = 0.04). H19 expression was significantly upregulated in IS and remained high for 72 h after stroke. ROC curves showed that H19 expression within the first 24 h from stroke onset might serve as a biomarker for the early diagnosis of IS with 79.49% sensitivity and 80.00% specificity. H19 expression in small vessel occlusion (SVO) and large-artery atherosclerosis (LAA) patients were 3.74 and 3.34 times higher than the undetermined (UD) subtype, respectively [OR = 3.74 95% CL (1.14–12.27) P = 0.030 and OR = 3.34 95% CL (1.13–9.85) P = 0.029]. Conclusion The rs217727 polymorphism of the H19 is correlated with IS susceptibility, and H19 expression levels were higher in SVO and LAA patients. The upregulation of H19 may be considered as a diagnostic biomarker in IS among the Iranian population, but it cannot serve as a useful prognostic marker.

2020 ◽  
Author(s):  
Mohadese Rezaei ◽  
Mohammad Javad Mokhtari ◽  
Mahnaz Bayat ◽  
Anahid Safari ◽  
Mehdi Dianatpuor ◽  
...  

Abstract Background: Efforts to identify potential biomarkers for the diagnosis of ischemic stroke (IS) are valuable. The H19 gene plays a functional role in increasing the prevalence of IS risk factors. We evaluated the correlation between H19 rs217727 polymorphism and the expression level of H19 lncRNA with susceptibility to IS among the Iranian population.Methods: Blood samples were collected from IS patients (n = 114) and controls (n = 114). We concentrated on the expression pattern of H19 at different time points (i.e., 0-24, 24-48, and 48-72 hours after stroke). The tetra-primer ARMS-PCR method was applied for DNA genotyping. We used the quantitative real-time PCR to evaluate H19 expression levels. Results: The rs217727polymorphism of H19 was related with IS susceptibility in the co-dominant (OR=2.92, 95% CI=0.91-10.92, P=0.04) and recessive models (OR=2.80, 95% CI=0.96-8.15, P=0.04). H19 expression was significantly upregulated in IS and remained high for 72 hours after stroke. ROC curves showed that H19 expression within the first 24 hours from stroke onset might serve as a biomarker for the early diagnosis of IS with 79.49% sensitivity and 80.00% specificity. H19 expression in SVO and LAA patients were 3.74 and 3.34 times higher than the UD subtype, respectively [OR=3.74 95% CL (1.14-12.27) P=0.030 and OR=3.34 95% CL (1.13-9.85) P=0.029].Conclusion: The rs217727 polymorphism of the H19 is correlated with IS susceptibility, and H19 expression levels were higher in SVO and LAA patients. The upregulation of H19 may be considered as a diagnostic biomarker in IS among the Iranian population.


2015 ◽  
Vol 73 (8) ◽  
pp. 648-654 ◽  
Author(s):  
Marcos C. Lange ◽  
Norberto L. Cabral ◽  
Carla H. C. Moro ◽  
Alexandre L. Longo ◽  
Anderson R. Gonçalves ◽  
...  

Aims To measure the incidence and mortality rates of ischemic stroke (IS) subtypes in Joinville, Brazil. Methods All first-ever IS patients that occurred in Joinville from January 2005 to December 2006 were identified. The IS subtypes were classified by the TOAST criteria, and the patients were followed-up for one year after IS onset. Results The age-adjusted incidence per 100,000 inhabitants was 26 (17-39) for large-artery atherosclerosis (LAA), 17 (11-27) for cardioembolic (CE), 29 (20-41) for small vessel occlusion (SVO), 2 (0.6-7) for stroke of other determined etiology (OTH) and 30 (20-43) for stroke of undetermined etiology (UND). The 1-year mortality rate per 100,000 inhabitants was 5 (2-11) for LAA, 6 (3-13) for CE, 1 (0.1-6) for SVO, 0.2 (0-0.9) for OTH and 9 (4-17) for UND. Conclusion In the population of Joinville, the incidences of IS subtypes were similar to those found in other populations. These findings highlight the importance of better detection and control of atherosclerotic risk factors.


2019 ◽  
Author(s):  
Lei Zhao ◽  
Jinghuan Fang ◽  
Muke Zhou ◽  
Jie Zhou ◽  
Lihua Yu ◽  
...  

Abstract Background Mutations of cyclooxygenase gene (COX gene) may increase the susceptibility of ischemic stroke. We investigated five variants (rs5788, rs1330344, rs3842788, rs20417, and rs689466) of two COX genes to explain the association between these polymorphisms and ischemic stroke risk determine whether gene–gene interaction between these genes increase the susceptibility of ischemic stroke or its subtypes. Methods A total of 1981 study subjects (1078 cases and 903 control subjects) were recruited. The interaction of multiple factors was investigated using Multifactor Dimensionality Reduction and additive effect of single nucleotide polymorphisms on ischemic stroke or its subtypes were analyzed by multiple factor logistic regression. Results At COX-1(rs1330344), AA genotype carriers had a lower susceptibility of ischemic stroke (OR=0.657, 95%CI= 0.437-0.988, P = 0.044), and A allele carriers had a lower susceptibility of ischemic stroke (OR=0.812, 95%CI= 0.657-0.978, P = 0.029). At COX-1(rs3842788), AA genotype carriers had a higher susceptibility of ischemic stroke (OR =5.203, 95% CI=1.519-5.159, P =0.016). At COX-2 (rs689466), AA genotype carriers had a higher susceptibility of large-artery atherosclerosis (OR =1.404, 95% CI=1.019-1.934, P =0.038). COX-1(rs1330344, rs3842788) and COX-2 rs689466 interacted in SVO, but had no additive effect with ischemic stroke or its subtypes. Conclusions At rs1330344, AA genotype may reduce the susceptibility of ischemic stroke. At rs3842788, AA genotype may increase the susceptibility of ischemic stroke. At rs689466, AA genotype may increase the susceptibility of large-artery atherosclerosis (LAA). COX-1(rs1330344, rs3842788) and COX-2 rs689466 interacted in small vessel occlusion (SVO), but had no additive effect with ischemic stroke or its subtypes.


Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Ryan McTaggart ◽  
Shadi Yaghi ◽  
Daniel C Sacchetti ◽  
Richard Haas ◽  
Shawna Cutting ◽  
...  

Background: There is very limited data on the use of advanced neuroimaging to select patients with acute ischemic stroke and large vessel occlusion for intraarterial therapy beyond 6 hours from onset. Our aim is to report the outcome of patients with acute ischemic stroke and large artery occlusion who presented beyond 6 hours from onset, had favorable MRI imaging profile, and underwent mechanical embolectomy. Methods: This is a single institution retrospective study between December 1st, 2015, and July 30 th , 2016 with acute ischemic stroke and anterior circulation large vessel occlusion (LVO) with ASPECTS of 6 or more and beyond 6 hours from symptoms onset. Favorable imaging profile was defined as 1) DWI lesion volume (as defined as apparent diffusion coefficient < 620 X 10-6 mm2/s) of 70 mL or less AND 2) Penumbra volume (as defined by volume of tissue with Tmax >6 sec) of 15 mL or greater AND 3) A mismatch ratio of 1.8 or more AND 4) Volume of tissue with perfusion lesion with Tmax > 10 sec is less than 100 mL. Good outcome was defined as a 90 day mRS≤2. Results: In the study period, 41 patients met the inclusion criteria; 22 (53.6%) had favorable imaging profile and underwent mechanical embolectomy. The median age was 75 years (59-92), 68.2% were females; the median time from last known normal to groin puncture was 684.5 minutes (range 363-1628) and the median admission NIHSS score was 17.5 (range 4-28). The rate of good outcomes in this series was similar to that in a patient level pooled meta-analysis of the recent endovascular trials (68.2% vs. 46.0%, p=0.07). The rate of good outcome matches that of the EXTEND-IA trial that selected patients using perfusion imaging (68.2% vs. 71.0%, p = 1.00). None of the patients in our cohort had symptomatic intracereberal hemorrhage. Conclusion: Advanced MR imaging may help select patients with acute ischemic stroke and anterior circulation large vessel occlusion for embolectomy beyond the treatment window used in most endovascular trials.


Stroke ◽  
2012 ◽  
Vol 43 (suppl_1) ◽  
Author(s):  
JUN LEE ◽  
Na-Young Kim

Background The relationship between stroke and non-atrial fibrillation cardiac arrhythmias remains unclear. Frequent premature ventricular contractions (PVCs) are associated with impaired ventricular relaxation and may increase the risk of clot formation and subsequent embolization. This study investigated the relationship between frequency of PVCs and etiologic subtypes of ischemic stroke. Methods Consecutive ischemic stroke patients admitted within 7 days of onset who underwent 24-hour Holter monitoring were enrolled (n=451). Subtypes of ischemic stroke were defined according to the SSS-TOAST classification as Large artery atherosclerosis (LAD), cardioembolic stroke (CE), small vessel occlusion (SVO), other causes (OC), and cryptogenic stroke (CS). Risk factors, demographic information, and 24-hour Holter recordings were compared between the subtypes of ischemic stroke. Results There were 182 women and 269 men (191 LAD, 90 CE, 93 SVO, 13 OC, 64 CS), with a mean age of 66 years (median 68). PVCs were seen in 305 patients (67.5%) on 24-hour Holter monitoring (median 3, IQR 0-48). CE had a higher median number of PVCs (median 24, IQR 0-258) than LAD (median 2, p=0.01), SVO (median 1, p<0.001), OC (median 0, p=0.013), and CS (median 4, p=0.2). The proportions of frequent PVCs (>50 in a 24-hour Holter monitoring) were higher in CE (43.3%) compared with the other groups (20.9% in LAD, 15.1% in SVO, 15.4% in OC, and 23.4% in CS; p<0.001). Compared with the SVO, the upper 3 quartiles of PVCs were associated with CE (OR 2.93; 95% CI, 1.69 to 5.06) and CS (OR 1.86; 95% CI, 1.07 to 3.2) in ordinal logistic regression analysis after adjustment for traditional risk factors. Conclusions The number of PVCs detected by 24-hour Holter monitoring is associated with CE and CS. The presence of high frequency of PVC may help in stratifying patients with different stroke subtypes, particularly embolic stroke. The role of these arrhythmias as a risk marker for ischemic stroke deserves further investigation.


Stroke ◽  
2019 ◽  
Vol 50 (7) ◽  
pp. 1805-1811 ◽  
Author(s):  
Susumu Kobayashi ◽  
Shingo Fukuma ◽  
Tatsuyoshi Ikenoue ◽  
Shunichi Fukuhara ◽  
Shotai Kobayashi ◽  
...  

Background and Purpose— In Japan, nearly half of ischemic stroke patients receive edaravone for acute treatment. The purpose of this study was to assess the effect of edaravone on neurological symptoms in patients with ischemic stroke stratified by stroke subtype. Methods— Study subjects were 61 048 patients aged 18 years or older who were hospitalized ≤14 days after onset of an acute ischemic stroke and were registered in the Japan Stroke Data Bank, a hospital-based multicenter stroke registration database, between June 2001 and July 2013. Patients were stratified according to ischemic stroke subtype (large-artery atherosclerosis, cardioembolism, small-vessel occlusion, and cryptogenic/undetermined) and then divided into 2 groups (edaravone-treated and no edaravone). Neurological symptoms were evaluated using the National Institutes of Health Stroke Scale (NIHSS). The primary outcome was changed in neurological symptoms during the hospital stay (ΔNIHSS=NIHSS score at discharge−NIHSS score at admission). Data were analyzed using multivariate linear regression with inverse probability of treatment weighting after adjusting for the following confounding factors: age, gender, and systolic and diastolic blood pressure at the start of treatment, NIHSS score at admission, time from stroke onset to hospital admission, infarct size, comorbidities, concomitant medication, clinical department, history of smoking, alcohol consumption, and history of stroke. Results— After adjusting for potential confounders, the improvement in NIHSS score from admission to discharge was greater in the edaravone-treated group than in the no edaravone group for all ischemic stroke subtypes (mean [95% CI] difference in ΔNIHSS: −0.46 [−0.75 to −0.16] for large-artery atherosclerosis, −0.64 [−1.09 to −0.2] for cardioembolism, and −0.25 [−0.4 to −0.09] for small-vessel occlusion). Conclusions— For any ischemic stroke subtype, edaravone use (compared with no use) was associated with a greater improvement in neurological symptoms, although the difference was small (<1 point NIHSS) and of limited clinical significance.


2016 ◽  
Vol 39 (6) ◽  
pp. 2353-2363 ◽  
Author(s):  
Man Zhu ◽  
Jiangcheng Zuo ◽  
Ji Shen ◽  
Wei Jing ◽  
Ping Luo ◽  
...  

Background: Ischemic stroke (IS) is an extremely heterogeneous disease with variable pathogenesis. Due to the lack of early diagnostic marker, the mortality rate of IS remains high worldwide. The family of Homer plays an important role in the pathology of atherosclerotic plaque. In this study, we have investigated its expression pattern and clinical significance in IS. Methods: RT-qPCR was performed to detect the expression of Homer1, Homer2, and Homer3. Results: We found that the mRNA levels of Homer1 (p<0.001) and Homer2 (p<0.001), but not Homer3, in large-artery atherosclerosis (LAA) strokes were significantly upregulated than those in non-LAA strokes and controls. Multinomial logistic regression analyses showed that, although none of the Homer was associated with non-LAA strokes, higher Homer1 (adjusted OR=1.337, 95% CI: 1.227-1.458) and Homer2 (adjusted OR=1.099, 95% CI: 1.062-1.138) levels showed significant associations with increased odds of having LAA stroke, compared with the controls. The receiver operating characteristic (ROC) curves showed that the combination of Homer1 and Homer2 had a better diagnostic accuracy to differentiate LAA strokes from non-LAA strokes and controls, and the sensitivity and specificity ratios were 80.5%/90.4% and 98.0%/70.3%, respectively. Conclusion: Our data suggested that Homer1 and Homer2 might be considered as novel diagnostic biomarkers for LAA stroke.


2016 ◽  
Vol 9 (6) ◽  
pp. 529-534 ◽  
Author(s):  
Waleed Brinjikji ◽  
Sharon Duffy ◽  
Anthony Burrows ◽  
Werner Hacke ◽  
David Liebeskind ◽  
...  

Background and purposeStudying the imaging and histopathologic characteristics of thrombi in ischemic stroke could provide insights into stroke etiology and ideal treatment strategies. We conducted a systematic review of imaging and histologic characteristics of thrombi in acute ischemic stroke.Materials and methodsWe identified all studies published between January 2005 and December 2015 that reported findings related to histologic and/or imaging characteristics of thrombi in acute ischemic stroke secondary to large vessel occlusion. The five outcomes examined in this study were (1) association between histologic composition of thrombi and stroke etiology; (2) association between histologic composition of thrombi and angiographic outcomes; (3) association between thrombi imaging and histologic characteristics; (4) association between thrombi imaging characteristics and angiographic outcomes; and (5) association between imaging characteristics of thrombi and stroke etiology. A meta-analysis was performed using a random effects model.ResultsThere was no significant difference in the proportion of red blood cell (RBC)-rich thrombi between cardioembolic and large artery atherosclerosis etiologies (OR 1.62, 95% CI 0.1 to 28.0, p=0.63). Patients with a hyperdense artery sign had a higher odds of having RBC-rich thrombi than those without a hyperdense artery sign (OR 9.0, 95% CI 2.6 to 31.2, p<0.01). Patients with a good angiographic outcome had a mean thrombus Hounsfield unit (HU) of 55.1±3.1 compared with a mean HU of 48.4±1.9 for patients with a poor angiographic outcome (mean standard difference 6.5, 95% CI 2.7 to 10.2, p<0.001). There was no association between imaging characteristics and stroke etiology (OR 1.13, 95% CI 0.32 to 4.00, p=0.85).ConclusionsThe hyperdense artery sign is associated with RBC-rich thrombi and improved recanalization rates. However, there was no association between the histopathological characteristics of thrombi and stroke etiology and angiographic outcomes.


2020 ◽  
Vol 40 (6) ◽  
Author(s):  
Lei Zuo ◽  
Cai Li ◽  
Juan Zu ◽  
Honghong Yao ◽  
Fuling Yan

Abstract Identifying those patients who were at high risk of stroke associated infection (SAI) for preventive antibiotic therapy was imperative for patients’ benefits, thus improving prediction of SAI was critical for all acute ischemic stroke (AIS) patients. Circular RNA FUNDC1 (circFUNDC1) has been reported to be the diagnosis and prognosis biomarker of AIS. Therefore, the present study aimed to figure out whether circFUNDC1 could be the potential predictor of SAI that could help to guide preventive treatment. In total, 68 patients were included in the study, 26 of which had infection and 42 without. Copy number of circFUNDC1 in plasma were quantified by quantitative real-time polymerase chain reaction (qPCR). Platelet spike-in experiment and correlation analysis were conducted to explore possible origins of circFUNDC1 in plasma. A significantly elevated level of circFUNDC1 was found in SAI patients compared with not infected AIS patients (P=0.0258). Receiver operating characteristic (ROC) curves demonstrated the prediction significance of circFUNDC1, with the area under the curve (AUC) at 0.6612 and sensitivity, specificity at 69.23%, 61.90% respectively in predicting SAI. Then, when adding circFUNDC1 in the risk model, the AUC increased from 0.7971 in model A to 0.8038 in model B. Additionally, positive correlation was observed between circFUNDC1 level and neutrophils counts. WBC and neutrophil ratios were significantly elevated in SAI patients compared with non-SAI patients. Therefore, circFUNDC1 could be used to construct a risk model for the prediction of SAI that is beneficial for AIS patients’ preventive treatment.


2016 ◽  
Vol 117 (2-3) ◽  
pp. 90-97 ◽  
Author(s):  
Hamid Reza Kouhpayeh ◽  
Mohsen Taheri ◽  
Mana Baziboroon ◽  
Mohammad Naderi ◽  
Gholamreza Bahari ◽  
...  

Cysteine-cysteine chemokine ligand 5 (CCL5) with immunoregulatory and inflammatory activities has an important role in granuloma formations that activates and stimulates T-cells and macrophages. Cysteine-cysteine chemokine receptor 5 (CCR5) is a chemokine receptor, which is important for migration of immune cells to site of infection. In the present study we investigated the possible association between CCL5 –403G/A (rs2107538), CCL5 –28C/G (rs2280788) and CCR5 Δ32 polymorphisms and pulmonary tuberculosis (PTB) in an Iranian population. This case-control study was performed on 160 patients with pulmonary tuberculosis and 160 unrelated healthy subjects. The CCL5 –403G/A, CCL5 –28C/G and CCR5 Δ32 polymorphisms were genotyped by allele-specific polymerase chain reaction (AS-PCR), tetra amplification refractory mutation system polymerase chain reaction (T-ARMS PCR) and PCR, respectively. Our results showed that GA as well as GA+AA genotypes of CCL5 –403G/A (rs2107538) increased the risk of PTB in comparison with GG genotype (OR=1.70, 95% CI=1.03–2.81, P=0.038 and OR=1.64, 95% CI=1.00–2.68, P=0.049, respectively). No significant association was found between CCL5 –28C/G as well as CCR5 Δ32 polymorphism and PTB risk. In conclusion, our findings proposed that CCL5 –403G>A polymorphism may be a risk factor for susceptibility to PTB in our population. Larger sample sizes with different ethnicities are required to validate our findings.


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