Rare Coding Variation and Risk of Intracerebral Hemorrhage.
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ABSTRACT:
SUBMITTER: Radmanesh F
PROVIDER: S-EPMC4519408 | biostudies-literature | 2015 Aug
REPOSITORIES: biostudies-literature
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Project description:Intracerebral hemorrhage (ICH), a subtype of stroke, can lead to long-term disability and is one of the leading causes of death. Unfortunately, the effectiveness of pharmacological therapy for ICH is still uncertain. Long non-coding RNA (lncRNA) was defined as an RNA molecule that consists of more than 200 nt without translational activity. As a vital class of diverse molecules, lncRNAs are involved in developmental and pathological processes and have been attractive for decades. LncRNAs have also become potential targets for therapies, as they were massively identified and profiled. In particular, emerging evidence has revealed the critical role of lncRNAs in ICH while attempts were made to treat ICH via regulating lncRNAs. But the latest evidence remains to be summarized. Thus, in this review, we will summarize the recent advances in lncRNA in ICH, highlighting the regulatory role of lncRNAs and their potential as therapeutic targets.
| S-EPMC10292654 | biostudies-literature
Project description:ImportanceBlack and Hispanic individuals have an increased risk of intracerebral hemorrhage (ICH) compared with their White counterparts, but no large studies of ICH have been conducted in these disproportionately affected populations.ObjectiveTo examine the prevalence, odds, and population attributable risk (PAR) percentage for established and novel risk factors for ICH, stratified by ICH location and racial/ethnic group.Design, setting, and participantsThe Ethnic/Racial Variations of Intracerebral Hemorrhage Study was a case-control study of ICH among 3000 Black, Hispanic, and White individuals who experienced spontaneous ICH (1000 cases in each group). Recruitment was conducted between September 2009 and July 2016 at 19 US sites comprising 42 hospitals. Control participants were identified through random digit dialing and were matched to case participants by age (±5 years), sex, race/ethnicity, and geographic area. Data analyses were conducted from January 2019 to May 2020.Main outcomes and measuresCase and control participants underwent a standardized interview, physical measurement for body mass index, and genotyping for the ɛ2 and ɛ4 alleles of APOE, the gene encoding apolipoprotein E. Prevalence, multivariable adjusted odds ratio (OR), and PAR percentage were calculated for each risk factor in the entire ICH population and stratified by racial/ethnic group and by lobar or nonlobar location.ResultsThere were 1000 Black patients (median [interquartile range (IQR)] age, 57 [50-65] years, 425 [42.5%] women), 1000 Hispanic patients (median [IQR] age, 58 [49-69] years; 373 [37.3%] women), and 1000 White patients (median [IQR] age, 71 [59-80] years; 437 [43.7%] women). The mean (SD) age of patients with ICH was significantly lower among Black and Hispanic patients compared with White patients (eg, lobar ICH: Black, 62.2 [15.2] years; Hispanic, 62.5 [15.7] years; White, 71.0 [13.3] years). More than half of all ICH in Black and Hispanic patients was associated with treated or untreated hypertension (PAR for treated hypertension, Black patients: 53.6%; 95% CI, 46.4%-59.8%; Hispanic patients: 46.5%; 95% CI, 40.6%-51.8%; untreated hypertension, Black patients: 45.5%; 95% CI, 39.%-51.1%; Hispanic patients: 42.7%; 95% CI, 37.6%-47.3%). Lack of health insurance also had a disproportionate association with the PAR percentage for ICH in Black and Hispanic patients (Black patients: 21.7%; 95% CI, 17.5%-25.7%; Hispanic patients: 30.2%; 95% CI, 26.1%-34.1%; White patients: 5.8%; 95% CI, 3.3%-8.2%). A high sleep apnea risk score was associated with both lobar (OR, 1.68; 95% CI, 1.36-2.06) and nonlobar (OR, 1.62; 95% CI, 1.37-1.91) ICH, and high cholesterol was inversely associated only with nonlobar ICH (OR, 0.60; 95% CI, 0.52-0.70); both had no interactions with race and ethnicity. In contrast to the association between the ɛ2 and ɛ4 alleles of APOE and ICH in White individuals (eg, presence of APOE ɛ2 allele: OR, 1.84; 95% CI, 1.34-2.52), APOE alleles were not associated with lobar ICH among Black or Hispanic individuals.Conclusions and relevanceThis study found sleep apnea as a novel risk factor for ICH. The results suggest a strong contribution from inadequately treated hypertension and lack of health insurance to the disproportionate burden and earlier onset of ICH in Black and Hispanic populations. These findings emphasize the importance of addressing modifiable risk factors and the social determinants of health to reduce health disparities.
| S-EPMC8383133 | biostudies-literature
Project description: Not available
| S-EPMC9194542 | biostudies-literature
Project description:ObjectivesRisk factors have been described for spontaneous intracerebral hemorrhage (ICH); their relative contribution to lobar vs nonlobar hemorrhage location is less clear. Our purpose here was to investigate risk factors by hemorrhage location.MethodsThis case-control study prospectively enrolled subjects with first-ever spontaneous ICH and matched each with up to 3 controls by age, race, and gender. Conditional stepwise logistic regression modeling was used to determine significant independent risk factors for lobar and nonlobar ICH.ResultsFrom December 1997 through December 2006, 597 cases and 1,548 controls qualified for the analysis. Hypertension, warfarin use, first-degree relative with ICH, personal history of ischemic stroke, less than a high school education, and APOE ε2 or ε4 genotype were more common in ICH cases. Hypercholesterolemia and moderate alcohol consumption (≤ 2 drinks per day) were less common in ICH cases. The associations of hypertension and hypercholesterolemia were specific for nonlobar ICH. Conversely, the association of APOE ε2 or ε4 genotype was specific for lobar ICH.ConclusionsAPOE ε2 or ε4 genotype was associated specifically with lobar ICH. Hypertension was associated specifically with nonlobar ICH. A protective association was seen between hypercholesterolemia and nonlobar ICH; no such association was identified for lobar ICH.
| S-EPMC3542348 | biostudies-literature
Project description:ObjectiveTo analyze the dose-risk relationship for alcohol consumption and intracerebral hemorrhage (ICH) in the Ethnic/Racial Variations of Intracerebral Hemorrhage (ERICH) study.MethodsERICH is a multicenter, prospective, case-control study, designed to recruit 1,000 non-Hispanic white patients, 1,000 non-Hispanic black patients, and 1,000 Hispanic patients with ICH. Cases were matched 1:1 to ICH-free controls by age, sex, race/ethnicity, and geographic area. Comprehensive interviews included questions regarding alcohol consumption. Patterns of alcohol consumption were categorized as none, rare (<1 drink per month), moderate (?1 drink per month and ?2 drinks per day), intermediate (>2 drinks per day and <5 drinks per day), and heavy (?5 drinks per day). ICH risk was calculated using the no-alcohol use category as the reference group.ResultsMultivariable analyses demonstrated an ordinal trend for alcohol consumption: rare (odds ratio [OR] 0.57, p < 0.0001), moderate (OR 0.65, p < 0.0001), intermediate (OR 0.82, p = 0.2666), and heavy alcohol consumption (OR 1.77, p = 0.0003). Subgroup analyses demonstrated an association of rare and moderate alcohol consumption with decreased risk of both lobar and nonlobar ICH. Heavy alcohol consumption demonstrated a strong association with increased nonlobar ICH risk (OR 2.04, p = 0.0003). Heavy alcohol consumption was associated with significant increase in nonlobar ICH risk in black (OR 2.34, p = 0.0140) and Hispanic participants (OR 12.32, p < 0.0001). A similar association was not found in white participants.ConclusionsThis study demonstrated potential protective effects of rare and moderate alcohol consumption on ICH risk. Heavy alcohol consumption was associated with increased ICH risk. Race/ethnicity was a significant factor in alcohol-associated ICH risk; heavy alcohol consumption in black and Hispanic participants poses significant nonlobar ICH risk.
| S-EPMC5440244 | biostudies-literature
Project description:Multiple sclerosis is a complex neurological disease, with ?20% of risk heritability attributable to common genetic variants, including >230 identified by genome-wide association studies. Multiple strands of evidence suggest that much of the remaining heritability is also due to additive effects of common variants rather than epistasis between these variants or mutations exclusive to individual families. Here, we show in 68,379 cases and controls that up to 5% of this heritability is explained by low-frequency variation in gene coding sequence. We identify four novel genes driving MS risk independently of common-variant signals, highlighting key pathogenic roles for regulatory T cell homeostasis and regulation, IFN? biology, and NF?B signaling. As low-frequency variants do not show substantial linkage disequilibrium with other variants, and as coding variants are more interpretable and experimentally tractable than non-coding variation, our discoveries constitute a rich resource for dissecting the pathobiology of MS.
| S-EPMC6269166 | biostudies-literature
Project description:Intracerebral hemorrhage (ICH) is a life-threatening condition associated with significant morbidity and mortality. Understanding the molecular mechanisms underlying ICH and its severe form is crucial for developing effective therapeutic strategies. This study investigates transcriptomic alterations in rodent models of ICH and severe intracerebral hemorrhage to shed light on the genetic pathways involved in hemorrhagic brain injury. We performed principal component analysis, revealing distinct principal component segments of normal rats compared to intracerebral hemorrhage and severe intracerebral hemorrhage rats. We further employed heatmaps and volcano plots to identify differentially expressed genes and utilized bar plots and KEGG pathway analysis to elucidate the different molecular pathways involved. Using comprehensive RNA sequencing and bioinformatics analyses, we identified a multitude of differentially expressed genes in both the ICH and severe ICH models. Our results revealed 5679 common genes among the normal, intracerebral hemorrhage, and severe intracerebral hemorrhage groups in the upregulated genes group, and 1196 common genes in the downregulated genes. A volcano plot comparing the groups further highlighted common genes, including PDPN, TIMP1, SERPINE1, TUBB6, and CD44. These findings underscore the complex interplay of genes involved in inflammation, oxidative stress, and neuronal damage. Furthermore, pathway enrichment analysis uncovered key signaling pathways, including the TNF signaling pathway, protein processing in the endoplasmic reticulum, MAPK signaling pathway, and Fc gamma R-mediated phagocytosis, implicated in the pathogenesis of ICH.
2024-06-11 | GSE264394 | GEO
Project description:BACKGROUND AND PURPOSE:Apolipoprotein E (ApoE) genotypes have been associated with lobar intracerebral hemorrhage (ICH). Although statins have been associated with an increased risk of ICH, meta-analyses have not consistently shown a statin-induced risk of ICH. Here, we test whether hypercholesterolemia (HC) and ApoE polymorphisms affect the risk of ICH by statin use. METHODS:The Genetic and Environmental Risk Factors for Hemorrhagic Stroke (GERFHS) study is a prospective, demographically matched case-control study of ICH. A similar study of ICH, Genetic Risks for Medication-Related Hemorrhagic Stroke (GOCHA), was used as a replication cohort. Subjects were classified as normocholesterolemia, HC without statin use, and HC with statin use. Statistical comparisons were performed using Fisher exact test, ?2 tests, and the Breslow-Day test. RESULTS:The discovery cohort consisted of 558 ICH cases and 1444 controls, and the replication cohort consisted of 1020 ICH cases and 382 controls. The association of lower risk for HC was not attenuated by statin use. Statin use was observed to confer a higher risk for lobar ICH in those carrying ApoE4/E4 and ApoE2/E4 genotypes in both discovery and replication cohorts, and a test for interaction showed a trend towards significance (P=0.11 for statin and ApoE4/E4). CONCLUSIONS:Statin use does not seem to attenuate the association of HC with decreased risk for nonlobar ICH. Our data support a gene-by-drug effect for lobar ICH, but larger sample sizes are needed to confirm the association before any clinical change is warranted. CLINICAL TRIAL REGISTRATION URL:http://clinicaltrials.gov. Unique identifier: NCT00930280.
| S-EPMC3873717 | biostudies-literature
Project description:Background and Purpose- The risk of arterial ischemic events after intracerebral hemorrhage (ICH) is poorly understood given the lack of a control group in prior studies. This study aimed to evaluate the risk of acute ischemic stroke and myocardial infarction (MI) among patients with and without ICH. Methods- We performed a retrospective cohort study using claims data from Medicare beneficiaries from 2008 to 2014. Our exposure was acute ICH, identified using validated International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis codes. Our primary outcome was a composite of acute ischemic stroke and MI, whereas secondary outcomes were ischemic stroke alone and MI alone. We used Cox regression analysis to compute hazard ratios during 1-month intervals after ICH. Sensitivity analyses entailed exclusion of patients with atrial fibrillation and valvular heart disease. Results- Among 1 760 439 Medicare beneficiaries, 5924 had ICH. The 1-year cumulative incidence of an arterial ischemic event was 5.7% (95% CI, 4.8-6.8) in patients with ICH and 1.8% (95% CI, 1.7-1.9) in patients without ICH. After adjusting for potential confounders, the risk of an arterial ischemic event remained significantly increased for the first 6 months after ICH and was especially high in the first month (hazard ratio, 6.7 [95% CI, 5.0-8.6]). In secondary analysis, the risk of ischemic stroke was increased in the first 6 months after ICH (hazard ratio, 6.1 [95% CI, 3.5-9.3]) but the risk of MI was not (hazard ratio, 1.6 [95% CI, 0.3-2.9]). In sensitivity analyses excluding patients with atrial fibrillation and valvular heart disease, the association between ICH and arterial ischemic events was similar to that of the primary analysis. Conclusions- In a large population-based cohort, we found that elderly patients with ICH had a substantially increased risk of ischemic stroke in the first 6 months after diagnosis. Further exploration of this risk is needed to determine optimal secondary prevention strategies for these patients.
| S-EPMC7001742 | biostudies-literature
Project description:Background and purposeRisk factors for infections after intracerebral hemorrhage (ICH) and their association with outcomes are unknown. We hypothesized there are predictors of poststroke infection and infections drive worse outcomes.MethodsWe determined prevalence of infections in a multicenter, triethnic study of ICH. We performed univariate and multivariate analyses to determine the association of infection with admission characteristics and hospital complications. We performed logistic regression on association of infection with outcomes after controlling for known determinants of prognosis after ICH (volume, age, infratentorial location, intraventricular hemorrhage, and Glasgow Coma Scale).ResultsAmong 800 patients, infections occurred in 245 (31%). Admission characteristics associated with infection in multivariable models were ICH volume (odds ratio [OR], 1.02/mL; 95% confidence interval [CI], 1.01-1.03), lower Glasgow Coma Scale (OR, 0.91 per point; 95% CI, 0.87-0.95), deep location (reference lobar: OR, 1.90; 95% CI, 1.28-2.88), and black race (reference white: OR, 1.53; 95% CI, 1.01-2.32). In a logistic regression of admission and hospital factors, infections were associated with intubation (OR, 3.1; 95% CI, 2.1-4.5), dysphagia (with percutaneous endoscopic gastrostomy: OR, 3.19; 95% CI, 2.03-5.05 and without percutaneous endoscopic gastrostomy: OR, 2.11; 95% CI, 1.04-4.23), pulmonary edema (OR, 3.71; 95% CI, 1.29-12.33), and deep vein thrombosis (OR, 5.6; 95% CI, 1.86-21.02), but not ICH volume or Glasgow Coma Scale. Infected patients had higher discharge mortality (16% versus 8%; P=0.001) and worse 3-month outcomes (modified Rankin Scale ≥3; 80% versus 51%; P<0.001). Infection was an independent predictor of poor 3-month outcome (OR, 2.6; 95% CI, 1.8-3.9).ConclusionsThere are identifiable risk factors for infection after ICH, and infections predict poor outcomes.
| S-EPMC4245453 | biostudies-literature