Intracerebral Hemorrhage Genetics

Ekkert, Aleksandra; Šliachtenko, Aleksandra; Utkus, Algirdas; Jatužis, Dalius

doi:10.3390/genes13071250

Cited by 13 publications

(9 citation statements)

References 85 publications

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“…Another possible explanation for our findings is that some subtypes of ischemic stroke present additional phenotypic dilemmas, such as the cardiogenic stroke subtype, whereas the phenotype of ICH is more uniform ( 71 ). Moreover, genetic factors are important in the pathogenesis of ICH ( 72 ). It is estimated that up to 44% of cases of ICH are heritable, and possessing an ICH first-degree relative increases the risk of developing the condition by a factor of six ( 73 ).…”

Section: Discussionmentioning

confidence: 99%

Stroke and the risk of gastrointestinal disorders: A Mendelian randomization study

Song

Chen²,

Ye³

2023

Front. Neurol.

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BackgroundThe issue of whether a stroke is causally related to gastrointestinal disorders was still not satisfactorily understood. Therefore, we investigated if there is a connection between stroke and the most prevalent gastrointestinal disorders, including peptic ulcer disease (PUD), gastroesophageal reflux disease (GERD), irritable bowel syndrome (IBS), and inflammatory bowel disease (IBD).MethodsWe applied two-sample Mendelian randomization to investigate relationships with gastrointestinal disorders. We obtained genome-wide association study (GWAS) summary data of any stroke, ischemic stroke, and its subtypes from the MEGASTROKE consortium. From the International Stroke Genetics Consortium (ISGC) meta-analysis, we acquired GWAS summary information on intracerebral hemorrhage (ICH), including all ICH, deep ICH, and lobar ICH. Several sensitivity studies were performed to identify heterogeneity and pleiotropy, while inverse-variance weighted (IVW) was utilized as the most dominant estimate.ResultsNo evidence for an effect of genetic predisposition to ischemic stroke and its subtypes on gastrointestinal disorders were found in IVW. The complications of deep ICH are a higher risk for PUD and GERD. Meanwhile, lobar ICH has a higher risk of complications for PUD.ConclusionThis study provides proof of the presence of a brain–gut axis. Among the complications of ICH, PUD and GERD were more common and associated with the site of hemorrhage.

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Section: Discussionmentioning

confidence: 99%

Stroke and the risk of gastrointestinal disorders: A Mendelian randomization study

Song

Chen²,

Ye³

2023

Front. Neurol.

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“…Several studies have reported the relationship between genetic factors and the risk of hemorrhagic stroke. 16 Such as, angiotensin converting enzyme (ACE) I/D polymorphism may increase the risk of hemorrhagic stroke. 17 Polymorphism of ADH1B was related to the risk of hemorrhagic stroke in a Taiwanese population.…”

Section: Discussionmentioning

confidence: 99%

ALDH2 rs671 Polymorphism Likely a Risk Factor for Hemorrhagic Stroke: A Hospital-Based Study

Zhang¹,

Wei-wen²,

Pan³

et al. 2023

IJGM

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Background Hypertension is the main risk factor for hemorrhagic stroke. Aldehyde dehydrogenase 2 (ALDH2) may inhibit the occurrence of hypertension by anti-oxidative stress and vascular dilation. The purpose was to investigate the relationship of ALDH2 polymorphisms with hemorrhagic stroke in Hakka Chinese. Methods A total of 329 patients with hemorrhagic stroke and 515 controls were enrolled, and medical records (smoking and drinking history, hypertension, and diabetes) were collected. The genotypes of ALDH2 rs671 of the two groups were detected and analyzed. Results The proportion of the ALDH2 rs671 G/G, G/A, and A/A genotype in patients with hemorrhagic stroke was 55.9%, 37.4%, and 6.7%, respectively, while those were 65.0%, 30.7%, and 4.3% in controls, respectively. There was statistically significant difference in ALDH2 rs671 genotypes distribution ( P =0.021) and alleles distribution ( P =0.005) between patients and controls. Among hemorrhagic stroke patients, no statistically significant differences were observed between patients with ALDH2 different genotypes. Logistic regression analysis showed that there was significantly high risk of hemorrhagic stroke in men (male vs female: adjusted OR 1.711, 95% CI 1.154–2.538, P =0.008), the presence of hypertension (with vs without hypertension: adjusted OR 16.095, 95% CI 10.958–23.641, P <0.001), and the presence of ALDH2 rs671 G/A genotype (G/A vs G/G: adjusted OR 1.679, 95% CI 1.151–2.450, P =0.007) or A/A genotype (A/A vs G/G: adjusted OR 2.516, 95% CI 1.132–5.591, P =0.024). Conclusion ALDH2 rs671 polymorphism likely a risk factor for hemorrhagic stroke.

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“…studies have shown that gene expression changes at the site of hemorrhage are focused on common genes and pathways. 14,22 Meanwhile, ICH's impact on molecular networks, including both pro-inflammatory and anti-inflammatory systems, offers insights into secondary injury mechanisms. 21,23 However, direct assessments of specific cell types in WMI models are still lacking.…”

Section: Despite the Clinical And Genetic Heterogeneity Of Ich Numerousmentioning

confidence: 99%

“… 9 , 10 The aftermath of hemorrhage includes activation of microglia cells, infiltration of inflammatory cells, and cytokine release, contributing to further WM injury (WMI). 11 , 12 These underlying processes present challenges for modeling and treatment, due to the condition's heterogeneity, 13 , 14 and a comprehensive understanding remains elusive.…”

Section: Introductionmentioning

confidence: 99%

Unraveling the complex pathophysiology of white matter hemorrhage in intracerebral stroke: A single‐cell RNA sequencing approach

Ye,

Tang,

Zhong

et al. 2024

CNS Neurosci Ther

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AimThis study aims to elucidate the cellular dynamics and pathophysiology of white matter hemorrhage (WMH) in intracerebral hemorrhage (ICH).MethodsUsing varying doses of collagenase IV, a consistent rat ICH model characterized by pronounced WMH was established. Verification was achieved through behavioral assays, hematoma volume, and histological evaluations. Single‐cell suspensions from the hemorrhaged region of the ipsilateral striatum on day three post‐ICH were profiled using single‐cell RNA sequencing (scRNA‐seq). Gene Ontology (GO) and gene set variation analysis (GSVA) further interpreted the differentially expressed genes (DEGs).ResultsFollowing WMH induction, there was a notable increase in the percentage of myeloid cells and oligodendrocyte precursor cells (OPCs), alongside a reduction in the percentage of neurons, microglia, and oligodendrocytes (OLGs). Post‐ICH WMH showed homeostatic microglia transitioning into pro‐, anti‐inflammatory, and proliferative states, influencing lipid metabolic pathways. Myeloid cells amplified chemokine expression, linked with ferroptosis pathways. Macrophages exhibited M1 and M2 phenotypes, and post‐WMH, macrophages displayed a predominance of M2 phenotypes, characterized by their anti‐inflammatory properties. A surge in OPC proliferation aligned with enhanced ribosomal signaling, suggesting potential reparative responses post‐WMH.ConclusionThe study offers valuable insights into WMH's complex pathophysiology following ICH, highlighting the significance and utility of scRNA‐seq in understanding the cellular dynamics and contributing to future cerebrovascular research.

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Intracerebral Hemorrhage Genetics

Cited by 13 publications

References 85 publications

Stroke and the risk of gastrointestinal disorders: A Mendelian randomization study

Stroke and the risk of gastrointestinal disorders: A Mendelian randomization study

ALDH2 rs671 Polymorphism Likely a Risk Factor for Hemorrhagic Stroke: A Hospital-Based Study

Unraveling the complex pathophysiology of white matter hemorrhage in intracerebral stroke: A single‐cell RNA sequencing approach

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