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An Inflammatory Polymorphisms Risk Scoring System for the Differentiation of Ischemic Stroke Subtypes.

ABSTRACT: Inflammation has been associated with atherothrombotic stroke and recently with cardioembolic stroke. Different genetic risk factors have been specifically associated with the subtypes of ischemic stroke (cardioembolic, atherothrombotic, and lacunar). However, there are no studies that have generated genetic risk scores for the different subtypes of ischemic stroke using polymorphisms associated with inflammation.We have analyzed 68 polymorphisms of 30 inflammatory mediator genes in 2,685 subjects: 1,987 stroke cases and 698 controls. We generated a genetic scoring system with the most significant polymorphisms weighted by the odds ratio of every polymorphism and taken into consideration the stroke subtype.Three polymorphisms, rs1205 (CRP gene), rs1800779, and rs2257073 (NOS3 gene), were associated with cardioembolic stroke (p value <0.05). The score generated was only associated with the cardioembolic stroke subtype (p value: 0.001) and was replicated in an independent cohort (p value: 0.017). The subjects with the highest score presented a cardioembolic stroke in 92.2% of the cases (p value: 0.002).The genetics of inflammatory markers is more closely associated with cardioembolic strokes than with atherothrombotic or lacunar strokes. The genetic risk scoring system could be useful in the prediction and differentiation of ischemic stroke; however, it might be specific to particular ischemic stroke subtypes.

SUBMITTER: Muino E

PROVIDER: S-EPMC4556875 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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An Inflammatory Polymorphisms Risk Scoring System for the Differentiation of Ischemic Stroke Subtypes.

Muiño Elena E Krupinski Jurek J Carrera Caty C Gallego-Fabrega Cristina C Montaner Joan J Fernández-Cadenas Israel I

Mediators of inflammation 20150819

<h4>Unlabelled</h4>Inflammation has been associated with atherothrombotic stroke and recently with cardioembolic stroke. Different genetic risk factors have been specifically associated with the subtypes of ischemic stroke (cardioembolic, atherothrombotic, and lacunar). However, there are no studies that have generated genetic risk scores for the different subtypes of ischemic stroke using polymorphisms associated with inflammation.<h4>Methods</h4>We have analyzed 68 polymorphisms of 30 inflamma ...[more]

PMID: 26355258

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Project description:Ischemic stroke (IS) is the main cause of mortality and disability among the old people in China and is a multifactorial disease influenced by many factors including genetic factors like the allele for CYP 2J2. It has been demonstrated that CYP2J2 polymorphisms alter the transcriptional activity. However, studies on the association between CYP2J2-50G/T polymorphism and IS have reported conflicting results. Thus, our study aimed to examine the association between 4 variants in the CYP2J2 gene and the risk of IS and its subtypes, in the Chinese population.In this study, genotyping was performed by using polymerase chain reaction (PCR) sequencing for 202 IS patients and 206 age- and sex-matched controls. Odds ratios (ORs) and confidence interval (CI) were estimated by multivariate logistic regression and PCR results were confirmed by DNA sequencing. A meta-analysis was conducted to evaluate the association of CYP2J2-50G>T polymorphism with the risk of IS in Chinese population by calculating pooled OR.We found this polymorphism was significantly associated with IS (17.82% vs. 10.68%, P = 0.039). Multiple logistic regression analysis revealed that GT genotype was associated with a significantly high risk of IS (OR = 2.32, 95% CI: 1.21-4.45, P = 0. 011) after adjustment for other confounding factors such as hypertension, diabetes, heart disease, smoking habit, family history, triglyceride and low-density lipoprotein levels. We also found a significant association of GT genotype with small artery occlusion (SAA) (P < 0.05; OR = 2.22; 95% CI: 1.043-4.72). Meta-analysis results also showed that the GT genotype carriers had a negative effect on the risk of IS in Chinese population with overall OR of 1.40 (95% CI: 1.06-1.84).The findings of the present study suggested that polymorphism in -50G/T position of CYP2J2 gene might be a risk factor for IS in Chinese population. Further large prospective studies were required to confirm these findings.

Project description:Background and purposeTo identify the qualitative and quantitative contributions of conventional risk factors for occurrence of ischemic stroke and its key pathophysiologic subtypes among West Africans.MethodsThe SIREN (Stroke Investigative Research and Educational Network) is a multicenter, case-control study involving 15 sites in Ghana and Nigeria. Cases include adults aged ≥18 years with ischemic stroke who were etiologically subtyped using the A-S-C-O-D classification into atherosclerosis, small-vessel occlusion, cardiac pathology, other causes, and dissection. Controls were age- and gender-matched stroke-free adults. Detailed evaluations for vascular, lifestyle, and psychosocial factors were performed. We used conditional logistic regression to estimate adjusted odds ratios with 95% CI.ResultsThere were 2431 ischemic stroke case and stroke-free control pairs with respective mean ages of 62.2±14.0 versus 60.9±13.7 years. There were 1024 (42.1%) small vessel occlusions, 427 (17.6%) large-artery atherosclerosis, 258 (10.6%) cardio-embolic, 3 (0.1%) carotid dissections, and 719 (29.6%) undetermined/other causes. The adjusted odds ratio (95% CI) for the 8 dominant risk factors for ischemic stroke were hypertension, 10.34 (6.91-15.45); dyslipidemia, 5.16 (3.78-7.03); diabetes, 3.44 (2.60-4.56); low green vegetable consumption, 1.89 (1.45-2.46); red meat consumption, 1.89 (1.45-2.46); cardiac disease, 1.88 (1.22-2.90); monthly income $100 or more, 1.72 (1.24-2.39); and psychosocial stress, 1.62 (1.18-2.21). Hypertension, dyslipidemia, diabetes were confluent factors shared by small-vessel, large-vessel and cardio-embolic subtypes. Stroke cases and stroke-free controls had a mean of 5.3±1.5 versus 3.2±1.0 adverse cardio-metabolic risk factors respectively (P<0.0001).ConclusionsTraditional vascular risk factors demonstrate important differential effect sizes with pathophysiologic, clinical and preventative implications on the occurrence of ischemic stroke among indigenous West Africans.

Project description:ImportanceThe risk for low-trauma fracture is increased by more than 30% after ischemic stroke, but existing fracture risk scores do not account for history of stroke as a high-risk condition.ObjectiveTo derive a risk score to predict the probability of fracture within 1 year after ischemic stroke and validate it in a separate cohort.Design, setting, and participantsPrognostic study of a cohort from the Ontario Stroke Registry, a population-based sample of adults in Ontario, Canada, who were hospitalized with ischemic stroke from July 1, 2003, to March 31, 2012, with 1 year of follow-up. A population-based validation cohort consisted of a sample of 13 698 consecutive stroke admissions captured across 5 years: April 2002 to March 2003, April 2004 to March 2005, April 2008 to March 2009, April 2010 to March 2011, and April 2012 to March 2013.ExposuresPredictor variables were selected based on biological plausibility and association with fracture risk. Age, sex, and modified Rankin score were abstracted from the medical records part of the Ontario Stroke Audit, and other characteristics were abstracted from administrative health data.Main outcomes and measuresIncidence of low-trauma fracture within 1 year of discharge, based on administrative health data.ResultsThe Fracture Risk after Ischemic Stroke (FRAC-Stroke) Score was derived in 20 435 patients hospitalized for ischemic stroke (mean [SD] age, 71.6 [14.0] years; 9564 [46.8%] women) from the Ontario Stroke Registry discharged from July 1, 2003, to March 31, 2012, using Fine-Gray competing risk regression. Low-trauma fracture occurred within 1 year of discharge in 741 of the 20 435 patients (3.6%) in the derivation cohort. Age, discharge modified Rankin score (mRS), and history of rheumatoid arthritis, osteoporosis, falls, and previous fracture were associated with the cumulative incidence of low trauma fracture in the derivation cohort. Model discrimination in the validation cohort (n = 13 698) was good (C statistic, 0.70). Discharge mRS was an important discriminator of risk (relative integrated discrimination improvement, 8.7%), with highest risk in patients with mRS 3 and 4 but lowest in bedbound patients (mRS 5). From the lowest to the highest FRAC-Stroke quintile, the cumulative incidence of 1-year low-trauma fracture increased from 1.3% to 9.0% in the validation cohort. Predicted and observed rates of fracture were similar in the external validation cohort. Analysis was conducted from July 2016 to January 2019.Conclusions and relevanceThe FRAC-Stroke score allows the clinician to identify ischemic stroke survivors at higher risk of low-trauma fracture within 1 year of hospital discharge. This information might be used to select patients for interventions to prevent fractures.

Dataset Information

An Inflammatory Polymorphisms Risk Scoring System for the Differentiation of Ischemic Stroke Subtypes.

Publications

An Inflammatory Polymorphisms Risk Scoring System for the Differentiation of Ischemic Stroke Subtypes.

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