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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. [ABSTRACT FROM AUTHOR]

Previously published studies that have examined whether the three polymorphisms, G894T, T786C, and 4b/a in the endothelial nitric oxide synthase (eNOS) gene, are associated with ischemic stroke (IS) have reported conflicting results. Thus, we performed a meta-analysis to examine the potential association between these three single nucleotide polymorphisms (SNPs) of the eNOS gene and IS risk. A literature search was carried out for eligible candidate gene studies published before August 05, 2015 in the PubMed, Embase, and Google Scholar databases. The following combinations of main keywords were used in our study: ('endothelial nitric oxide synthase') or ('eNOS') and ('G894T, 4b/a, and T786C') and ('polymorphism') or ('polymorphisms') and ('Ischemic Stroke' or 'IS') and ('Cerebral Infarction' or 'CI') and ('genetic polymorphism' or 'single nucleotide polymorphisms' or 'SNP'). Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by using fixed or random effects model. Meta-regression analysis was used to investigate the potential sources of heterogeneity. Begg's funnel plots were used to explore the publication bias, and heterogeneity was assessed by I2 test. Twenty seven case-control studies involving 6733 cases and 7305 controls were analyzed in our meta-analysis. Significant association was observed for G894T (OR = 1.17; 95% CI: 1.08 to 1.28; P< 0.001) and 4b/a (OR = 1.25; 95% CI: 1.13 to 1.39; P < 0.001) whereas a non-significant association was observed for T786C (OR = 1.11; 95% CI: 0.98 to 1.26; P =0.109) eNOS gene polymorphisms and IS. Our meta-analysis establishes that the G894T and 4b/a polymorphisms of eNOS gene are significantly associated with the risk of IS. However, a non-significant association was found between T786C polymorphism of the eNOS gene and IS risk. Further prospective large epidemiological studies need to be done to confirm these findings. [ABSTRACT FROM AUTHOR]

Stroke, a heterogeneous multifactorial disorder, is known to be a major cause of death and adult disability within both the developed and developing countries. Approximately 85% of stroke cases are ischemic, whereas the remaining 15% are hemorrhagic. It is caused by multiple genetic factors, environmental factors, and interactions among these factors. Several candidate genes have been found to be associated with ischemic stroke. The most extensively studied genes include those involved in hemostasis, inflammation, nitric oxide production, homocysteine and lipid metabolism, and rennin-angiotensin-aldosterone system. Combined linkage/association studies have demonstrated that genes encoding phosphodiesterase 4D (PDE4D) and arachidonate 5-lipoxygenase-activating protein (ALOX5AP) confer risk for stroke. Even though there is substantial evidence for the genetic basis of stroke as provided by the epidemiological data from twin- and family-based studies, the contribution of genetic factors identified till now is either not enough or very less to explain the entire spectrum of encountered phenomena associated with ischemic stroke. Till date, no genome-wide association studies (GWAS) have been carried out in India. We aim to extensively review the studies on candidate genes that may have potential applications in the early diagnosis, prevention, and treatment of ischemic stroke in the Indian population. This article further emphasizes the role of GWAS in ischemic stroke and the need for an extensive GWAS in the Indian population. [ABSTRACT FROM AUTHOR]

Background: Stroke is a multifactorial, polygenic disorder, influenced by both environmental and genetic factors. Aim: The purpose of this study was to determine the association of beta-1 and beta-2 adrenergic receptor (AR) polymorphisms with intracerebral hemorrhagic stroke (ICH) in a North Indian population. Materials and Methods: One hundred and six patients with intracerebral hemorrhage (ICH) and 106 age- and sex-matched controls were recruited. Genotyping was performed by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. RFLP results of three samples of each genotype were confirmed by DNA sequencing. Results: Mean age of cases and controls were 53.47 ± 14 and 52.92 ± 13.4, respectively. Significant association between Ser49Gly polymorphism of beta-1 AR and ICH in patients who had onset of disease at a later stage of life (>50 years) under a dominant model of inheritance (OR, 3.6; 95% 1.4 to 9.7) was observed. Under the dominant model of inheritance, Gln27Glu polymorphism of beta-2 AR was associated with risk of ICH (OR, 3.2; 95% CI, 1.7 to 5.8) and significant association persisted even after adjustment for demographic and other risk factor variables (OR, 2.9; 95% CI, 1.04 to 8; P = 0.04). Age-stratified analysis showed an independent significant association of Gln27Glu polymorphism of beta-2 AR with risk of ICH in patients those had onset of disease at young age (<50 years) under a dominant model of inheritance (OR, 3.5; 95% CI, 1.1 to 11). Conclusion: The present study provides the first preliminary evidence that Gln27Glu polymorphism of beta-2 AR may contribute modest effect in increase in risk of ICH in North Indian Population. Large prospective studies with large sample size are required to confirm these findings. [ABSTRACT FROM AUTHOR]

Background: Several observational studies have reported the prevalence of cerebral microbleeds (CMBs) and their risk factors in an elderly population. Any information in this regard is currently lacking from India. Aim of this study was to estimate the prevalence, risk factors of CMBs, and association with cognition in an Indian urban population aged 50 years and above. Methods: Household surveys were conducted as part of ongoing Longitudinal Cognition and Aging Research on Population of the National Capital Region (LoCARPoN) study in areas of urban Delhi. Magnetic resonance imaging of the brain was performed in 2599 participants. Using standard neuropsychological battery, mean Z-scores for each domain (memory, executive, information) were derived. Binary and stepwise logistic regression models were used to determine associated risk factors for the presence of CMB and its association with cognitive domains. Results: The prevalence of CMBs was 14.42% (95% confidence interval [CI]: 13.06-15.73). Of these, 203 (7.81%) participants had single CMBs and 172 (6.61%) had multiple microbleeds (≥2). Higher prevalence was observed in older age (6070 years: odds ratio [OR]: 1.25 [95% CI: 0.93-1.67]; 70-80 years: OR: 2.05 [95% CI: 1.48-2.84]; ≥80 years: OR: 3.27 [95% CI: 1.97-5.44]) compared to individuals in the age group 50-60 years. History of stroke (OR: 2.97 [95% CI: 1.56-5.66]), hypertension (OR: 1.36 [95% CI: 1.05-1.75]), and smoking (OR: 1.43 [95% CI: 1.11-1.85]) was associated with at least one CMB. Multiple CMBs were associated with worse scores in memory and executive domains. Conclusion: Older age, hypertension, history of stroke, and history of smoking emerged as important risk factors for the presence of multiple CMBs. Follow-up study is required to determine implications of CMBs. [ABSTRACT FROM AUTHOR]

Background: Spontaneous intracerebral hemorrhage (SICH) accounts for 7.5%-30% of all strokes and carries higher morbidity and mortality. Raised blood urea nitrogen and creatinine ratio (BUNR) is a marker of dehydration and related to poor outcome in stroke patients. However, the ratio varies between 15 and 80 in different studies. The aim of the present study was to assess BUNR as an independent predictor of mortality and its sensitivity and specificity in predicting outcome in the SICH population.Materials and Methods: Patients above the age of 18 years with SICH who were admitted in the Department of Neurology at Sir Sunderlal Hospital, Banaras Hindu University between January 2018 and July 2020 were enrolled in the study and prospectively followed up. Demographic, clinical, radiological, and outcome parameters were recorded.Results: A total of 217 patients were included. Of these, 137 (63%) were males. Seventy-one patients died during the initial 30 days. Number of patients with intraventricular hemorrhage (IVH; P = 0.003), higher mean intracerebral hemorrhage (ICH) volume (P < 0.001) and midline shift (P = 0.021), and poor Glasgow Coma Scale (GCS) score (<9) (P = 0.040) was more in the group which did not survive. Mean level of urea was significantly lower among survivors than in those who died (P = 0.001). BUNR was also significantly higher in those who died than in those who survived (P = 0.001). BUNR with a cutoff value of 39.17 was significantly associated with mortality at 30 days with a sensitivity and specificity of 61.97% and 62.33%, respectively. On performing two different multivariable logistic studies, it was found that model B with BUNR ratio as a predictor of mortality out performed model A (without BUNR).Conclusions: The study showed that SICH was associated with significant mortality. Independent predictors of death at 30 days were lower GCS on admission, larger hematoma volume, and BUNR of more than 39.17. [ABSTRACT FROM AUTHOR]

Introduction: Genetic factors may play a role in the susceptibility of intracerebral hemorrhage (ICH). The present case-control study hypothesized that genetic polymorphisms in tumor necrosis factor- α (TNF-α) gene may affect the risk of ICH.Materials and Methods: In this study, we investigated the association of four single nucleotide polymorphisms (-308G/A, +488G/A, -857C/T, and -1031T/C) within TNF-α gene promoter and their haplotypes with the risk of ICH in a North Indian population. Genotyping was determined by using the SNaPshot method for 100 ICH patients and 100 age and sex-matched ICH-free controls. Conditional logistic regression analysis with adjusting multiple demographic and risk factor variables was used to calculate the strength of association between TNF-α gene polymorphisms and risk of ICH. Haplotypes were reconstructed using PHASE 2.0, and patterns of linkage disequilibrium (LD) analysis were performed using Haploview version 4.2 software.Results: TNF-α +488G/A gene polymorphism was found to be independently associated with the risk of ICH under dominant [GG + GA vs. AA] (OR = 3.1; 95% CI = 1.2-8.2; P = 0.001) and allelic [G vs. A] (OR = 2.2; 95% CI = 1.2-4.2; P = 0.007) models. However, no significant association between -308G/A, -857C/T, and -1031T/C gene polymorphisms and risk of ICH was observed. Haplotype analysis showed that 308A-488G-857C-1031T and 308G-488A-857T-1031T haplotypes were significantly associated with an increased risk of ICH. Strong LD was observed for + 488G/A and -857C/T TNF-α polymorphisms (D' = 0.72, r2= 0.01).Conclusion: Our findings suggest that the TNF-α +488G/A polymorphism may be an important risk factor for ICH, whereas -308G/A, -857C/T, and -1031T/C gene polymorphisms may not be associated with risk of ICH in North Indian population. [ABSTRACT FROM AUTHOR]

Background: Stroke is the second largest cause of mortality (WHO 2014) and long lasting disability worldwide. Many risk factors are associated with stroke, such as age, gender, chronic illnesses, cardiovascular disease, lifestyle, and smoking. With global industrialization, the roles of environmental contaminants and their association with stroke are still unclear and have attracted much more attention. Materials and Methods: We conducted a systematic review on the environmental toxic metal contaminants and the risk of ischemic stroke. A comprehensive literature search was carried out till June 30, 2021 from databases such as PubMed, Science Direct, Embase, and Scopus. The quality of all the articles which met our inclusion criteria was assessed using Newcastle--Ottawa scaling, and four eligible studies were included for our systematic review. Results: The serum and urine cadmium concentrations were positively associated with the risk of ischemic stroke. There was an inverse association of serum and urine concentrations of mercury (Hg), serum concentration of gold and cerium with ischemic stroke, and the serum and urine concentrations of lead (Pb) had no association with ischemic stroke risk. Conclusion: The study showed strong associations between heavy metals and ischemic stroke, but more studies are required to prove the associations. [ABSTRACT FROM AUTHOR]