Stroke In Iranian Population Research Articles

Protein C Promotor Haplotypes Associated with Large-Artery Atherosclerosis Stroke in Iranian Population.

Ischemic stroke (IS) is a complex disease regarding its risk factors; among those factors, genetics has an important role. Protein C (PC) is an important antithrombotic enzyme which its genetic variations disrupt the normal cascade of blood coagulation, resulting in thrombosis and increases the chance of stroke. Therefore, we aimed to investigate three single-nucleotide polymorphisms (SNPs) located in the core promoter of PC in order to find their role in this condition in the Iranian population. Blood samples from IS patients (n=249) and healthy volunteers (n=203) were collected. Biochemical analysis was performed. Genotyping was conducted on the extracted DNA from blood samples via the HRM technique. Bioinformatic investigations were used to assess how these SNPs may be involved in the IS. Smoking, hypertension, low-density lipoprotein cholesterol, and fasting blood glucose were significantly different between healthy and IS groups. rs1799809 and rs1799810 SNPs were significantly more frequent among IS patients. Also, among four identified haplotypes, CGT was found associated with IS (p=0.001). It was also found that these SNPs may interfere with the binding of transcription factors to alter the expression of PC. Our data predict that SNPs at the core promoter of PC can affect the binding affinity of transcription factors which in turn reduces the expression of PC and increases the risk of IS.

A Comprehensive Systematic Review and Meta-analysis on the Risk Factors of Stroke in Iranian Population.

There are limited data on vascular risk factors (VRFs) in low- and middle-income countries (LMICs). This meta-analysis was completed to summarize the existing evidence on stroke risk factors (SRFs) in the Iranian population. An electronic literature search of the databases including PubMed, Embase, Web of Science, Scopus, Scientific Information Database (SID), Magiran, and IranMedex was performed to identify the related articles published up to March 2018. For categorical or continuous variables, the data were also pooled using the fixed- or the random-effect models, respectively, expressed as odds ratio (OR) or weighted mean difference (WMD). A total of 15 articles were recruited. The risk of stroke was associated with mean age, but not gender. Among traditional VRFs, hypertension (HTN), systolic and diastolic blood pressure (DBP), diabetes mellitus (DM), and fasting blood glucose (FBG) were associated with increased risk of stroke. Apart from the high circulating levels of triglycerides (TG), low-density lipoprotein-cholesterol (LDL-C), total cholesterol (TC), and low high-density lipoprotein-cholesterol (HDL-C), other potential risk factors namely cigarette smoking (CS), opioid addiction (OD), and waist circumference (WC) were identified to be independent stroke determinants. The present systematic review and meta-analysis provided a summary of the most important SRFs, which are potentially modifiable and preventable. Overall, Iran, similar to many other LMICs, is experiencing an ever-increasing rate of stroke-prone elderly people. The LMICs are thus suggested to develop national approaches to recognize and address VRFs, to monitor and control CS and OD rates, and to encourage a healthy lifestyle.

Is carotid artery stenting without protection safe? - A single center experience: case series

Background: Carotid artery stenosis is one of the main causes of ischemic stroke in Iranian population. Carotid artery stenting (CAS) is a method with for treating carotid artery disease, in order to prevent stroke. Dispersion of the embolus is a significant risk for carotid angioplasty which can be prevented by using protective devices. But studies have shown that the use of these protective devices is not safe and can have side effects such as vascular spasm and dissection. Method: 36 patients who underwent unprotected carotid artery angioplasty from April 2018 to August 2019 in Shahid Madani hospital retrospectively entered this study. Hospital records were studied for data collection. Patients were followed by phone interviews. Major adverse cardiovascular and cerebral events (MACCE) was defined as a composite of the occurrence of stroke, MI, bleeding, and all-cause mortality in the long term. Mean duration of our follow-up was 6 months. Results: During in-hospital course, an 82 years old woman with a history of CVA, hypertension, diabetes and a significant stenosis in her contralateral ICA, had an episode of stroke which was fatal. Also, there was a 46 years old woman without any risk factors, who had developed intracranial hemorrhage (ICH). 22 patients were followed. No MI, stroke, or death occurred in any of the patients. There were only 2 cases of bleeding. Conclusion: Carotid artery stenting without protection may be is a safe method of carotid revascularization. Further prospective studies and clinical trials are needed.

Association of lymphotoxin-alpha gene polymorphisms (rs909253, rs1800683 and rs2229094) and risk of large-artery atherosclerosis stroke in Iranian population.

Lymphotoxin-alpha (LTA), a proinflammatory cytokine, is significantly associated with the progression of atherosclerosis as an independent hazard factor for stroke. According to new genetic studies, polymorphisms in the LTA gene that influence its expression or biological function may play a role in the progress of stroke; thus, the present case-control study investigated LTA gene polymorphisms (rs909253, rs1800683 and rs2229094) and the risk of large artery atherosclerosis stroke (LAA) in an Iranian population. For 211 large artery atherosclerosis patients and 186 ischemic stroke-free controls, genotypes were determined using the tetra-primer amplification-refractory mutation system polymerase chain reaction method. Linkage disequilibrium and estimated haplotypes were analyzed using SNP Analyzer 2 software. The strength of the link between LTA gene polymorphisms (rs1800683, rs909253, and rs2229094) and the risk of stroke was determined using conditional logistic regression. Analysis revealed that the patterns of the rs1800683, rs909253 and rs2229094 genotypes showed no significant difference between the LAA and control group, although the distribution of the GAT (rs1800683G, rs909253A and rs2229094T) haplotype was significantly higher in the control group (odds ratio = 0.707, 95% confidence interval = 0.53-0.942, p = 0.0355). Our results indicate that the GAT haplotype in LTA gene is associated with a decreased risk of LAA incidence in a northeastern Iranian population.

Association between methylene tetrahydrofolate reductase polymorphisms and risk of ischemic stroke

Background: The methylene tetrahydrofolate reductase (MTHFR) is a folate-dependent enzyme which catalyzes the conversion of homocysteine to methionine. Two single nucleotide polymorphisms (SNPs) within this gene namely rs1801133 (C677T) and rs1801131 (A1298C) have been associated with elevated risk of ischemic stroke and total serum homocysteine in some populations.Aim: To assess associations between MTHFR SNPs and risk of ischemic stroke in Iranian population.Methods: In the current case-control study, we genotyped rs1801133 and rs1801131 SNPs in 318 Iranian patients with history of ischemic stroke and 400 age- and sex-matched controls using tetra-primer amplification refractory mutation system-polymerase chain reaction method.Results: The rs1801133 was significantly associated with risk of stroke in recessive model (OR (95% CI) = 1.89 (1.12–3.20), p = 0.03). The CT haplotype (rs1801131 and rs1801133, respectively) was significantly over-represented in patients compared with controls (OR (95% CI) = 1.71 (0.25–2.32), p = 0.002).Conclusion: Consequently, our data demonstrate contribution of MTHFR variants in risk of ischemic stroke in Iranian population.

GRM7 polymorphisms are not associated with ischemic stroke in Iranian population

Objectives: Ischemic stroke is the main neurological cause of acquired incapability in adults and a prominent cause of mortality. Several association studies have been conducted to explore the role of candidate genes in this neurological condition.Methods: In the present study, we aimed at identification of association between Glutamate Metabotropic Receptor 7 (GRM7) and risk of ischemic stroke in Iranian population. Two intronic variants within this gene (rs6782011 and rs779867) were genotyped in 318 sporadic ischemic stroke cases and 300 unrelated, healthy controls individuals.Results: No significant difference was found in allele, genotype or haplotype frequencies of these SNPs between cases and controls after correction for multiple comparisons.Conclusion: Consequently, the assessed GRM7 variants are not implicated in risk of ischemic stroke in Iranian population.

Associations Between Two Single-Nucleotide Polymorphisms in NINJ2 Gene and Risk of Psychiatric Disorders.

NINJ2 encodes a transmembrane protein that contributes in neurodevelopment and regeneration of neurons. Single-nucleotide polymorphisms (SNPs) within this gene have been associated with Alzheimer's disease, ischemic stroke, and multiple sclerosis. The rs11833579 and rs3809263 SNPs have been associated with risk of ischemic stroke in Iranian population. While the NINJ2 rs12425791 has been with risk of ischemic stroke in East Asian population, the rs11833579 has not been associated with this condition either in East Asian population or Chinese Han population. In the current project, we genotyped rs11833579 and rs3809263 in a large cohort of neuropsychiatric patients including major depressive disorder, bipolar disorder, schizophrenia, and methamphetamine addiction. No significant difference was detected in frequencies of alleles, genotypes, or haplotypes between patients and controls. Thus, the current investigation failed to show association between rs11833579 and rs3809263 and the mentioned neuropsychiatric disorders. Future studies are needed to verify our results.

Association of 5-lipoxygenase activating protein gene polymorphism and stroke: A study from north east of Iran

Background: Stroke is a multifactorial disorder and a major cause of morbidity and mortality around the world. There are growing numbers of candidate gene pathways which are thought to be associated with stroke. Genes involved in lipid metabolism are important issues in stroke studies. Studying different polymorphisms in these genes are becoming an interest for researchers. 5-lipoxygenase activating protein (ALOX5AP) is one of these genes. Different studies have provided different relations between ALOX5AP promoter polymorphism (rs17222919) and stroke. In the present study, we have evaluated this gene polymorphism in a population in north east of Iran. Methods: This case-control study took place in Ghaem Hospital, Mashhad, Iran. Patients with computed tomography (CT) or magnetic resonance imaging (MRI) confirmation for ischemic stroke were enrolled in this study and considered as case group. Healthy persons without ischemic stroke were control group. During 1-year period of this study, ALOX5AP gene polymorphism in 200 healthy patients (control group) as well as 228 patients with stroke (case group) was evaluated by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results: All of 428 persons (228 cases and 200 healthy controls) enrolled in this study. The genotype and allele frequency was significantly different between both groups (P = 0.001 and P = 0.003, respectively). A total number of 54 patients had G allele in case group in contrast to 27 ones in control group. Also, 174 patients in case group had T allele and 173 persons had this allele in control group. In compression of TT genotype, the risk of developing stroke in GG and TG genotypes increased by 3.998 and 1.643, respectively. Also the risk of ischemic stroke with G allele would increase by 2.128. Conclusion: According to our results, ALOX5AP promoter polymorphism (rs17222919) is related to increased ischemic stroke in Iranian population.

Analysis of association between RAGE polymorphisms and stroke risk

Receptor for advanced glycation end products (RAGE) is a kind of immunoglobulins that interacts with several ligands and participates in regulation of immune responses. Variants within RAGE gene have been associated with risk of stroke in different populations. In the present study, we have assessed associations between two single nucleotide polymorphisms (SNPs) in this gene and risk of ischemic stroke in Iranian persons by using tetra primer-amplification refractory mutation system-PCR approach. Totally, 184 patients with history of ischemic stroke and 192 age- and sex-matched controls were recruited. After correction for multiple comparisons, there were no significant difference in allele frequencies of rs184003 and rs1800625 between cases and controls (P values of 0.38 and 0.06 respectively). A significant association was found between rs1800625 genotypes and risk of stroke in recessive and additive models (OR (95% CI) = 0.2 (0.04–0.93), adjusted P value = .04; OR (95% CI) = 1.52 (1.04–2.21), P value = .03 respectively) which implies that CC genotype has a protective role against stroke in the assessed population when compared with TT + CT genotypes. The estimated haplotypes distributed similarly between cases and controls. Our data propose a role for RAGE variants in modulating the risk of stroke in Iranian population. However, our data need to be appraised in larger cohorts of patients.

Genetic variants within Ninjurin 2 gene are associated with risk of ischemic stroke in Iranian population.

Previous genetic and epidemiological studies have shown the contribution of genetic factors in conferring the risk of ischemic stroke. Among the acknowledged risk factors of stroke are the single nucleotide polymorphisms (SNPs) near Ninjurin 2 (NINJ2) gene which encodes a surface adhesion protein. In the current study, we investigated the role of two SNPs near this gene in ischemic stroke in Iranian population. The frequency of the A allele of the rs11833579 was significantly lower in cases compared with controls (OR (95% CI) = 0.68 (0.54-0.86), adjusted P value = 0.002). The rs11833579 was significantly associated with risk of stroke in co-dominant (AA vs. GG: OR (95% CI) = 0.39 (0.23-0.66), adjusted P value = 0.003) and recessive (OR (95% CI) = 0.44 (0.27-0.72), adjusted P value = 0.001) models. The rs3809263 was associated with risk of stroke in dominant model (OR (95% CI) = 1.5 (1.09-2.06), adjusted P value = 0.02). The A C haplotype (rs11833579 and rs3809263) decreased the risk of stroke (OR (95% CI) = 0.72 (0.57-0.91), adjusted P value = 0.03), while the G T haplotype conferred susceptibility to stroke (OR (95% CI) = 1.42 (1.11-1.82), adjusted P value = 0.02). Consequently, the present case-control study supports the role of NINJ2 as a risk locus for ischemic stroke in Iranian population.

Quality of Life Within Three Months After Stroke: A Study in the City of Arak, Iran

IntroductionThe impact of stroke on quality of life (QoL) may be different in diverse societies because of varying availability and accessibility of health and social care services provided in various settings. The purpose of the present study was to evaluate changes in patients’ QoL within three months after stroke and to address the research question; “What factors influence QoL after stroke in Iranian population?” MethodsA total number of 172 patients admitted to the Stroke Unit of Amiralmomenin Hospital in the city of Arak, Iran, were recruited in this study. The Stroke Impact Scale (SIS-16) was used at three different time-points to evaluate post-stroke QoL. Repeated measures analysis of variance (ANOVA) followed by Bonferroni method and marginal model with generalized estimating equation (GEE) were employed to analyze the data. ResultsThe findings revealed a significant decline in QoL within the first month after stroke compared with post-stroke state. The mean values of patients' QoL also improved within three months after stroke although they did not reach the pre-stroke level. A positive relationship was also observed between age, high National Institutes of Health Stroke Scale (NIHSS) scores, hypertension, right side lesion and previous stroke, as well as patients’ poor QoL. Moreover; gender, level of education, job status, and income had no influence on QoL in stroke survivors. ConclusionIt was concluded that being older, having higher NIHSS score, suffering from hypertension, right side lesion and previous stroke could be significantly correlated with poor patients’ QoL. Therefore, effective interventions focusing on older individuals especially those with more severe impairments were assumed to help in improving post-stroke QoL in patients; regardless of their gender, level of education, and social activities.

Thromboxane A synthase 1 gene expression and promotor haplotypes are associated with risk of large artery-atherosclerosis stroke in Iranian population.

Large artery atherosclerosis (LAA) is known as an important cause of ischemic stroke (IS), which is a multifactorial disorder. Many candidate genes have been proposed for IS like (TBXAS1) that plays a significant role in LAA stroke pathogenesis. This is the first study on the evaluation of the association of the five single-nucleotide polymorphisms (SNPs) in TBXAS1 promoter region and the level of TBXAS1 transcript with large-artery atherosclerosis stroke. Five SNPs in TBXAS1 genes were investigated in 248 patients with large-artery atherosclerosis stroke and 199 healthy controls in Iranian population in this case-control study through using the high-resolution melting assay. In addition, the relationships between the selected SNPs with alteration of TBXAS1 gene expressions were investigated in terms of blood platelets through the reverse transcription-quantitative polymerase chain reaction. Multivariate logistic analysis with adjustments indicated that rs10256282CC, rs10237429CC, and rs4590360GG genotypes were associated with large-artery atherosclerosis stroke (adjusted odds ratio = 2.804, 2.872, and 2.432, respectively; P < 0.05, q < 0.05). Furthermore, the frequency of CACCG haplotype in the patients was greatly higher than that in the controls (OR = 1.424, 95% CI: 1.071-1.893, P = 0.014738). In addition, TBXAS1 expression was higher in patients compared to the controls (P = 0.021), and individuals with the homozygous mutated genotypes of these SNPs showed a higher expression level compared to other genotype (P < 0.05). In total, our findings indicate a significant association of TBXAS1 gene rs10256282CC, rs10237429CC, and rs4590360GG polymorphisms with large-artery atherosclerosis stroke susceptibility and the level of TBXAS1 expression, which was not previously reported in any population.

Association between human leucocyte antigen alleles and risk of stroke in Iranian population.

Previous studies have demonstrated associations between human leucocyte antigen (HLA) and some types of ischaemic stroke. In the present study, we genotyped HLA-A,-B and -DRB1 alleles in 140 Iranian patients with history of ischaemic stroke and 140 age-/sex-matched healthy subjects. No significant difference has been found in the distribution of HLA-A and B alleles between cases and controls. The DRB1*16 allele was significantly over-represented in patient group compared with control group (Adjusted p value=0.048). Other HLA-DRB1 alleles were not associated with stroke risk. The HLA-B*35,B*52 genotype was significantly more prevalent among patients compared with controls (Adjusted p value=0.03, OR [95% CI]=9.3 [1.3, 407.2]). Several HLA haplotypes were associated with risk of stroke in the assessed population. The current study provides further evidences for participation of HLA in conferring risk of ischaemic stroke.

The Streptokinase Therapy Complications and its Associated Risk Factors in Patients with Acute ST Elevation Myocardial Infarction.

Acute myocardial infarction (AMI) is one of the main leading causes of mortality and morbidity. Despite the progress in the treatment of AMI, streptokinase is still being used in many countries. Because of the critical condition of patients with AMI and complications of streptokinase therapy, this study was performed to evaluate the pattern of adverse drug reaction (ADRs) induced by streptokinase and its associated risk factors in patients with acute ST elevation MI. A prospective cross-sectional study in a 14-month period was done at the university affiliated referral cardiovascular center. The Naranjo probability scale and Food and drug administration (FDA) criteria for severity of ADRs were performed for assessing the ADRs. The linear and logistic regression tests were used to evaluate the correlation between ADRs and study risk factors. During the study period, 217 patients who received streptokinase were entered. The majority of patients (n = 191) experienced at least one ADR. Six patients died in-hospital mainly because of cardiac causes. The history of drug allergy was the main predictor in occurring of ADRs (Odds ratio: 3.26; 95% CI: 1.48-457.6; p =0.026). The most serious ADR was hemorrhagic stroke with a 1.4% incidence. Hypotension was one of the most occurred ADR (n = 75). Anaphylactic shock was not detected in this study. In summary, our study showed that the history of drug allergy is the main predictor in occurring of ADRs by streptokinase. Furthermore, streptokinase therapy was associated with a higher rate of hemorrhagic stroke in Iranian population.

Association Of Mir-196a (Rs11614913) And Mir-499 (Rs3746444) With Ischemic Stroke An Iranian Study

Objective: MicroRNAs are involved in the regulation of many physiological and pathological processes, such as atherosclerosis. Genetic polymorphisms in microRNA may affect its biogenesis and function. The aim of this study was to examine whether microRNA polymorphisms (mir-196a rs11614913 and mir-499 rs3746444) contribute to the risk of ischemic stroke. Methods: Genotyping was performed in 85 patients and 105 normal control, using polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) method.Results: In respect of rs11614913, significant association was observed between CC (P=0.003; OR= 0.41; CI=0.21 – 0.79), and TT (P=0.025; OR=2.22; CI=1.04 –4.8) genotypes. The inheritance of T allele increased the risk of ischemic stroke. There was a significant association between the GA genotype frequency of rs3746444 (P=0.01; OR= 0.41; CI=0.23– 0.87). TDiscussion: The present study provided evidence that the mir-196a and mir-499 polymorphisms are associated with a significantly increased risk of ischemic stroke in Iranian population. The common genetic polymorphism in pre-microRNAs may be contributed to the pathogenesis of ischemic stroke and represented as novel markers for stroke susceptibility.

Review of Stroke: The 2nd International and the 8th National Iranian Stroke Congress : Shiraz, Iran

Dear reader,&#x0D; Stroke is a major health problem in Iran as other developing countries. Meanwhile, epidemiological characteristics of stroke in Iranian population are different with other countries. Both  population-based and hospital-based studies showed that  incidence and mortality of stroke in Iran is higher than most western countries [1,2]. Higher rates of patients with young-adult stroke in Iranian population are a prominent feature too [3]. In the same time, prevalence of cerebral venous sinus thrombosis is higher than western populations [4] but the frequency of the intracranial stenosis is more or less same as Europeans [5]. The high prevalence of atherosclerotic disease in Iran can be attributed to social and economic factors, including increased life span, changes in dietary habits and an increasingly sedentary lifestyle [6]. In the light of these changes, Iranian health policymakers should consider concerted primary and secondary preventive measures to reduce the impact of this increasingly problematic public health issue.&#x0D; Iranians who have had a stroke consider their social, financial and rehabilitative support to be inadequate. Moreover, awareness of the manifestations of stroke is poor in the Iranian general population [7]. Consequently, the clinical status of stroke patients by the time they are transferred to the referral center may be worse than it could have been. There is an urgent need for Iranian hospitals to develop better measures to manage acute stroke patients.&#x0D; The second international Iranian stroke congress was held from 23-25 September 2015 in Shiraz, Iran. This Conference was a joint effort of the Clinical Neurology Research Center of Shiraz University of Medical Sciences and Iranian Stroke Association.&#x0D; Here we presented  some selected reviews from outstanding platforms of this congress. Ghandehari presented the epidemiology of stroke in Iran [8]. Safari et al presented a comprehensive review about immunology of stroke [9]. Abolhasani-Foroughi and Nazeri  summarized the role of Computed topography scan for diagnosis and treatment planning of stroke patients [10].&#x0D; Lotfi discussed about pearls and pitfalls of color doppler sonography of cervical arteries [11]. We also have three reviews about clinical and radiologic aspects of cerebral venous sinus thrombosis [12-14]. Two reviews focused on importance of rehabilitation in new stroke era [15,16].&#x0D; Â

Review of Stroke: The 2nd International and the 8th National Iranian Stroke Congress : Shiraz, Iran

Dear reader,Stroke is a major health problem in Iran as other developing countries. Meanwhile, epidemiological characteristics of stroke in Iranian population are different with other countries. Both population-based and hospital-based studies showed that incidence and mortality of stroke in Iran is higher than most western countries [1,2]. Higher rates of patients with young-adult stroke in Iranian population are a prominent feature too [3]. In the same time, prevalence of cerebral venous sinus thrombosis is higher than western populations [4] but the frequency of the intracranial stenosis is more or less same as Europeans [5]. The high prevalence of atherosclerotic disease in Iran can be attributed to social and economic factors, including increased life span, changes in dietary habits and an increasingly sedentary lifestyle [6]. In the light of these changes, Iranian health policymakers should consider concerted primary and secondary preventive measures to reduce the impact of this increasingly problematic public health issue.Iranians who have had a stroke consider their social, financial and rehabilitative support to be inadequate. Moreover, awareness of the manifestations of stroke is poor in the Iranian general population [7]. Consequently, the clinical status of stroke patients by the time they are transferred to the referral center may be worse than it could have been. There is an urgent need for Iranian hospitals to develop better measures to manage acute stroke patients.The second international Iranian stroke congress was held from 23-25 September 2015 in Shiraz, Iran. This Conference was a joint effort of the Clinical Neurology Research Center of Shiraz University of Medical Sciences and Iranian Stroke Association.Here we presented some selected reviews from outstanding platforms of this congress. Ghandehari presented the epidemiology of stroke in Iran [8]. Safari et al presented a comprehensive review about immunology of stroke [9]. Abolhasani-Foroughi and Nazeri summarized the role of Computed topography scan for diagnosis and treatment planning of stroke patients [10].Lotfi discussed about pearls and pitfalls of color doppler sonography of cervical arteries [11]. We also have three reviews about clinical and radiologic aspects of cerebral venous sinus thrombosis [12-14]. Two reviews focused on importance of rehabilitation in new stroke era [15,16].