Failure to validate association between 12p13 variants and ischemic stroke.
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ABSTRACT:
SUBMITTER: International Stroke Genetics Consortium
PROVIDER: S-EPMC2978046 | biostudies-literature | 2010 Apr
REPOSITORIES: biostudies-literature
Publications
Failure to validate association between 12p13 variants and ischemic stroke.
The New England journal of medicine 20100401 16
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Project description:Genetic variants in the gene encoding integrin alpha2 (ITGA2) have been reported to be associated with an increased risk for ischemic stroke. The purpose of this study was to investigate the association between haplotype-tagging single-nucleotide polymorphisms (tSNPs) in ITGA2 and risk of ischemic stroke in a collection of North American stroke cases and controls. The study included 484 cases and 263 controls. Thirteen tSNPs were genotyped. Association tests at and across each tSNP were performed, including haplotype association analysis. Secondary analyses considered stroke subtypes on the basis of Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria. We observed significant association between tSNP rs3756541 (additive model, odds ratio (OR), 1.49; 95% confidence interval (CI), 1.11 to 2.04; P=0.009) and disease and a trend toward association at rs2303124 (recessive model, OR, 1.56; 95% CI, 1.05 to 2.33; P=0.03). These associations remained significant in the haplotype analyses. The associated tSNPs did not distinguish stroke etiology after application of TOAST criteria. Our results suggest that genetic variability within ITGA2 may confer risk for ischemic stroke independent of conventional risk factors. These results provide additional support for a role for platelet receptor genes in the pathogenesis of ischemic stroke of diverse subtypes.
| S-EPMC2629802 | biostudies-literature
Project description:BACKGROUND: The association between ischemic stroke and 2 single nucleotide polymorphisms (SNPs) on chromosome 12p13, rs12425791 and rs11833579 appears inconsistent across different samples. These SNPs are close to the ninjurin2 gene which may alter the risk of stroke by affecting brain response to ischemic injury. The purpose of this study was to investigate the association between these two SNPs and ischemic stroke risk, as well as prognostic outcomes in a Taiwanese sample. METHODS: We examined the relations of these two SNPs to the odds of new-onset ischemic stroke, ischemic stroke subtypes, and to the one year risk of stroke-related death or recurrent stroke following initial stroke in a case-control study. A total of 765 consecutive patients who had first-ever ischemic stroke were compared to 977 stroke-free, age-matched controls. SNPs were genotyped by Taqman fluorescent allelic discrimination assay. The association between ischemic stroke and SNPs were analyzed by multivariate logistic regression. Cox proportional hazard model was used to assess the effect of individual SNPs on stroke-related mortality or recurrent stroke. RESULTS: There was no significant association between SNP rs12425791 and rs11833579 and ischemic stroke after multiple testing corrections. However, the marginal significant association was observed between SNP rs12425791 and large artery atherosclerosis under recessive model (OR, 2.30; 95%CI, 1.22-4.34; q-value = 0.062). Among the 765 ischemic stroke patients, 59 died or developed a recurrent stroke. After adjustment for age, sex, vascular risk factors and baseline stroke severity, Cox proportional hazard analysis indicated that the hazard ratios were 2.76 (95%CI, 1.34-5.68; q-value, 0.02) and 2.15 (95%CI, 1.15-4.02; q-value, 0.03) for individuals with homozygous variant allele of rs12425791 and rs11833579, respectively. CONCLUSIONS: This is a precedent study that found genetic variants of rs12425791 and rs11833579 on chromosome 12p13 are independent predictors of stroke-related mortality or stroke recurrence in patients with incident ischemic stroke in Taiwan. Further study is needed to explore the details of the physiological function and the molecular mechanisms underlying the association of this genetic locus with ischemic stroke.
| S-EPMC3269363 | biostudies-literature
Project description:ContextAlthough stroke centers are widely accepted and supported, little is known about their effect on patient outcomes.ObjectiveTo examine the association between admission to stroke centers for acute ischemic stroke and mortality.Design, setting, and participantsObservational study using data from the New York Statewide Planning and Research Cooperative System. We compared mortality for patients admitted with acute ischemic stroke (n = 30,947) between 2005 and 2006 at designated stroke centers and nondesignated hospitals using differential distance to hospitals as an instrumental variable to adjust for potential prehospital selection bias. Patients were followed up for mortality for 1 year after the index hospitalization through 2007. To assess whether our findings were specific to stroke, we also compared mortality for patients admitted with gastrointestinal hemorrhage (n = 39,409) or acute myocardial infarction (n = 40,024) at designated stroke centers and nondesignated hospitals.Main outcome measureThirty-day all-cause mortality.ResultsAmong 30,947 patients with acute ischemic stroke, 15,297 (49.4%) were admitted to designated stroke centers. Using the instrumental variable analysis, admission to designated stroke centers was associated with lower 30-day all-cause mortality (10.1% vs 12.5%; adjusted mortality difference, -2.5%; 95% confidence interval [CI], -3.6% to -1.4%; P < .001) and greater use of thrombolytic therapy (4.8% vs 1.7%; adjusted difference, 2.2%; 95% CI, 1.6% to 2.8%; P < .001). Differences in mortality also were observed at 1-day, 7-day, and 1-year follow-up. The outcome differences were specific for stroke, as stroke centers and nondesignated hospitals had similar 30-day all-cause mortality rates among those with gastrointestinal hemorrhage (5.0% vs 5.8%; adjusted mortality difference, +0.3%; 95% CI, -0.5% to 1.0%; P = .50) or acute myocardial infarction (10.5% vs 12.7%; adjusted mortality difference, +0.1%; 95% CI, -0.9% to 1.1%; P = .83).ConclusionAmong patients with acute ischemic stroke, admission to a designated stroke center was associated with modestly lower mortality and more frequent use of thrombolytic therapy.
| S-EPMC3290863 | biostudies-literature
Project description:The human cytochrome P450 (CYP) superfamily includes at least 57 genes that encode enzymes with diverse metabolic and biosynthetic functions. This study was conducted in order to investigate the associations between polymorphisms in CYP superfamily genes (CYP11B2, CYP17A1, CYP2B6, CYP2C9, CYP2E1 and CYP7A1) and ischemic stroke (IS). Six single nucleotide polymorphisms (SNPs) of CYP superfamily genes were selected and genotyped by direct sequencing in 121 patients with IS and 321 control subjects. The genetic data were analyzed using SNPStats and SPSS 18.0. Multiple logistic regression models (codominant 1, codominant 2, dominant, recessive and log-additive) were used to evaluate odds ratios (ORs), 95% confidence intervals (CIs) and p-values. The rs179998 SNP of CYP11B2 was significantly associated with IS (p=0.0336 in a log-additive model). The rs3813867 SNP of CYP2E1 was significantly associated with smoking in IS (p=0.0336 in a log-additive model). The rs1799998 SNP of CYP11B2 and rs3808607 of CYP7A1 were related to diabetes mellitus in IS (p<0.05). CYP11B2, CYP2E1 and CYP7A1 SNPs were associated with IS in the population studied. Further study is required to confirm these associations and to determine their biological significance.
| S-EPMC3438554 | biostudies-literature
Project description:BackgroundFew studies have examined the relationship between the amounts of heavy metal and stroke incidence. The aim of this study was to explore the relationship between levels of heavy metals, including Pb, Hg, As, and Cd, in patients with acute ischemic stroke (AIS).MethodsWe selected patients with first-ever AIS onset within 1 week as our study group. Healthy controls were participants without a history of stroke or chronic disease, except hypertension. The serum levels of Pb, Hg, As, and Cd in participants in the experimental and control groups were determined. All participants received a 1-g infusion of edetate calcium disodium (EDTA). Urine specimens were collected for 24 h after EDTA infusion and measured for heavy metal levels.ResultsIn total, 33 patients with AIS and 39 healthy controls were enrolled in this study. The major findings were as follows: (1) The stroke group had a significantly lower level of serum Hg (6.4 ± 4.3 μg/L vs. 9.8 ± 7.0 μg/L, P = 0.032, OR = 0.90, 95% CI = 0.81-0.99) and a lower level of urine Hg (0.7 ± 0.7 μg/L vs. 1.2 ± 0.6 μg/L, P = 0.006, OR = 0.27, 95% CI = 0.11-0.68) than the control group. (2) No significant difference in serum Pb (S-Pb), As (S-As), and Cd (S-Cd) levels and urine Pb (U-Pb), As (U-As) and Cd (U-Cd) levels was observed in either group.ConclusionsOur study found low levels of serum and urine Hg in first-ever patients with AIS, providing new evidence of dysregulated heavy metals in patients with AIS.
| S-EPMC5970463 | biostudies-literature
Project description:BackgroundMalnutrition is associated with a high risk of mortality in adults with ischemic stroke (IS). This study aimed to investigate the relationship between malnutrition and the risk of stroke-associated pneumonia (SAP) as only a few studies examined the relationship between malnutrition and the risk of SAP in IS.MethodsPatients were included from emergency departments of five tertiary hospitals in the REtrospective Multicenter study for Ischemic Stroke Evaluation (REMISE) study from January 2020 to December 2020. Malnutrition was defined according to the Controlling Nutritional Status (CONUT), Geriatric Nutritional Risk Index (GNRI), and Prognostic Nutritional Index (PNI) systems. Multivariable logistic regression analysis was used to explore the association between malnutrition and risk of SAP.ResultsWe enrolled 915 patients with IS, 193 (14.75%), 495 (54.1%), and 148 (16.2%) of whom were malnourished according to the PNI, CONUT, and GNRI scores, respectively. SAP occurred in 294 (32.1%) patients. After adjusting for confounding influencing factors in the logistic regression analysis, malnutrition (moderate and severe risk vs. absent malnutrition) was independently associated with an increased risk of SAP based on the PNI (odds ratio [OR], 5.038; 95% confidence interval [CI] 2.435-10.421, P < 0.001), CONUT (OR, 6.941; 95% CI 3.034-15.878, P < 0.001), and GNRI (OR, 2.007; 95% CI 1.186-3.119, P = 0.005) scores. Furthermore, adding malnutrition assessment indices to the A2DS2 score significantly improved the ability to predict SAP by analysis of receiver operating characteristic curves and net reclassification improvement.ConclusionMalnutrition was notably prevalent in patients with IS and independently associated with an increased risk of SAP. Further studies are required to identify the effect of interventions on malnutrition to reduce the risk of SAP.
| S-EPMC10399066 | biostudies-literature
Project description:ObjectivesIschemic stroke has long been a global health threat. Genetic factors, a looming risk for ischemic stroke, remain unexplored. The high-mobility group box 1 (HMGB1) protein showed a connection with the occurrence and development of ischemic stroke. This study was conducted to find whether frequent HMGB1 polymorphisms (rs1045411, rs1412125, and rs2249825) play a role in ischemic stroke susceptibility and recurrence risk.MethodsOur study was carried out in a Chinese Han population with a sample size of 871 patients and 858 age-matched healthy controls. Tag single nucleotide polymorphisms (tagSNPs) were selected by conventional protocols and DNA was extracted for genotype analysis after the participants had signed an informed consent. Comprehensive statistical analyses were conducted.ResultsIt was found that the C allele of the HMGB1 rs1412125 (OR = 1.263, 95% CI = 1.075-1.483, P = 0.004) and HMGB1 rs2249825 (adjusted OR = 2.464, 95% CI = 1.215-4.996, P = 0.012) variants was associated with a high risk of ischemic stroke, with the male subgroup carrying the TT allele of the HMGB1 rs1045411 variant tended to suffer more from the disease (adjusted OR = 3.600, 95% CI = 1.272-10.193, P = 0.016). A haplotype study also showed significant results (OR = 1.554, 95% CI = 1.246-1.938, P = 0.001). The rs1412125 polymorphism was highly associated with the chance of recurrence but not with the onset age (TC vs. TT: P = 0.034; CC vs. TT: P < 0.001). Cox regression analysis and stratified analysis were carried out with notable conclusions.ConclusionsOur study provided evidence for the association between HMGB1 polymorphisms and ischemic stroke susceptibility and recurrence, indicating that HMGB1 gene variants may be potential markers for first and secondary stroke prevention.
| S-EPMC10251027 | biostudies-literature
Project description:BackgroundReducing hospital readmission is an important goal to optimize poststroke care and reduce costs. Early outpatient follow-up may represent one important strategy to reduce readmissions. We examined the association between time to first outpatient contact and readmission to inform postdischarge transitions.Methods and resultsWe performed a retrospective cohort study of all Medicare fee-for-service patients discharged home after an acute ischemic stroke in 2012 identified by the InternationalClassification of Diseases, Ninth Revision, Clinical Modification codes. Our primary predictor variable was whether patients had a primary care or neurology visit within 30 days of discharge. Our primary outcome variable was all-cause 30-day hospital readmission. We used separate multivariable Cox models with primary care and neurology visits specified as time-dependent covariates, adjusted for numerous patient- and systems-level factors. The cohort included 78 345 patients. Sixty-one percent and 16% of patients, respectively, had a primary care and neurology visit within 30 days of discharge. Visits occurred a median (interquartile range) 7 (4-13) and 15 (5-22) days after discharge for primary care and neurology, respectively. Thirty-day readmission occurred in 9.4% of patients. Readmissions occurred a median 14 (interquartile range, 7-21) days after discharge. Patients who had a primary care visit within 30 days of discharge had a slightly lower adjusted hazard of readmission than those who did not (hazard ratio, 0.98; 95% confidence interval, 0.97-0.98). The association was nearly identical for 30-day neurology visits (hazard ratio, 0.98; 95% confidence interval, 0.97-0.98).ConclusionsThirty-day outpatient follow-up was associated with a small reduction in hospital readmission among elderly patients with stroke discharged home. Further work should assess how outpatient care may be improved to further reduce readmissions.
| S-EPMC5901901 | biostudies-literature
Project description:BackgroundObservational studies have shown an inverse association between circulating linoleic acid (LA) and risk of ischemic stroke (IS).ObjectiveThe aim of this study was to explore whether genetic variants predicting levels of circulating LA are associated with IS and its subtypes using a two-sample Mendelian randomization (MR) analysis.MethodsLA-related single-nucleotide polymorphisms (SNPs) were selected from a genome-wide association study of 8,631 participants, and summary statistics of IS and IS subtypes were obtained from the MEGASTROKE consortium. MR analysis was performed using the inverse-variance weighted (IVW) method complemented with other approaches, including weighted-median, weighted-mode, MR Pleiotropy RESidual Sum and Outlier test and MR-Egger regression, to test for the robustness of the association. Moreover, we conducted bidirectional MR analysis to assess the impact of IS-associated SNPs on circulating LA levels. Odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated.ResultsWe found that genetically predicted circulating LA levels were inversely associated with the risk of IS by the IVW method (OR = 0.98, 95% CI: 0.97-0.99, and P = 0.003). Subgroup analyses showed a statistically significant association between LA and risk of large artery stroke (LAS; OR = 0.95, 95% CI: 0.92-0.98, and P = 0.004), but not for other IS subtypes. The results were stable in sensitivity analyses, and no evidence of reverse association between LA and risk of IS, or LAS was observed.ConclusionOur study supports a potential inverse association of genetically predicted circulating LA levels with risk of IS, particularly LAS.
| S-EPMC7874191 | biostudies-literature
Project description:Neuronal expression of ATP-binding cassette, sub-family B (MDR/TAP), member 1 (ABCB1) has been demonstrated after brain ischemia. To investigate whether ABCB1 polymorphisms are associated with the development, risk factors (hypertension, dyslipidemia, and diabetes mellitus), severity (National Institutes of Health Stroke Scale, NIHSS), and sequelae (Modified Barthel Index, MBI) of ischemic stroke (IS), four single nucleotide polymorphisms (SNPs) of the ABCB1 gene [rs4148727, promoter, -154T>C; rs3213619, 5'-untranslation region (5'UTR), -129T>C); rs1128503, synonymous, Gly412 (C>T); rs3842, 3'UTR, A>G] were analyzed in 121 IS patients and 291 control subjects. SNPStats and SPSS 18.0 were used to obtain odds ratios (OR), 95% confidence intervals (CI), and p values. Multiple logistic regression models (codominant1, codominant2, dominant, recessive, and log-additive models) were applied to analyze the genetic data. The rs3842 SNP was weakly associated with the development of IS (p=0.020 in codominant1 model and p=0.028 in dominant model). In the analysis of clinical phenotypes, ABCB1 polymorphisms were nominally associated with hypertension (rs3213619 and rs3842, p<0.05), dyslipidemia (rs1128503, p<0.05), diabetes (rs3842, p<0.05), and NIHSS (rs4148727, p<0.05). Interestingly, rs3842 showed statistically strong association between IS with hypertension and IS without hypertension (Fisher's exact p=0.003, OR=0.11, 95% CI=0.03-0.51 in recessive model). These results suggest that the ABCB1 gene may be associated with the development and clinical phenotypes of IS in Korean population.
| S-EPMC3538181 | biostudies-literature