Dataset Information

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

ACCESS DATA

Publications

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

Similar Datasets

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: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.

Project description:Background and Purpose- The insulin sensitizer, pioglitazone, reduces cardiovascular risk in patients after an ischemic stroke or transient ischemic attack but increases bone fracture risk. We conducted a secondary analysis of the IRIS trial (Insulin Resistance Intervention After Stroke) to assess the effect of pretreatment risk for fracture on the net benefits of pioglitazone therapy. Methods- IRIS was a randomized placebo-controlled trial of pioglitazone that enrolled patients with insulin resistance but without diabetes mellitus within 180 days of an ischemic stroke or transient ischemic attack. Participants were recruited at 179 international centers from February 2005 to January 2013 and followed for a median of 4.8 years. Fracture risk models were developed from patient characteristics at entry. Within fracture risk strata, we quantified the effects of pioglitazone compared with placebo by estimating the relative risks and absolute 5-year risk differences for fracture and stroke or myocardial infarction. Results- The fracture risk model included points for age, race-ethnicity, sex, body mass index, disability, and medications. The relative increment in fracture risk with pioglitazone was similar in the lower (<median point score) and higher (? median point score) risk strata. However, the absolute risk difference (ARD) for fracture was less in the low-risk group (5.8% in pioglitazone group versus 4.0% in placebo group; ARD, 1.8%; 95% CI, -0.7% to 4.4%) compared with high-risk group (18.0% versus 11.6%; ARD, 6.4%; 95% CI, 3.2% to 9.6%). Reductions in risk for stroke or myocardial infarction did not vary by fracture risk (low-risk ARD, -3.7%; high-risk ARD, -3.5%). In low-risk patients, pioglitazone prevented 2.0 strokes or myocardial infarctions for each fracture caused, compared with 0.5 among those at high risk. Conclusions- A simple point score identifying patients at low risk for fracture may assist in selecting patients with a favorable benefit-risk profile for pioglitazone therapy after ischemic stroke or transient ischemic attack.

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.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure