ArticleStroke2013
Evidence HDAC9 genetic variant associated with ischemic stroke increases risk via promoting carotid atherosclerosis.
Article in Stroke, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers, 2 of them syntheses that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
65 citing papers in PubMed, 2 syntheses or guidelines pooled it, 112 citations in OpenAlex.
- Targeting epigenetics and non-coding RNAs in atherosclerosis: from mechanisms to therapeutics.Pharmacology & therapeutics · 2019Pooled it
- The association between HDAC9 gene polymorphisms and stroke risk in the Chinese population: A meta-analysis.Scientific reports · 2017Pooled it
- The relationship between the prognosis of children with acute arterial stroke and polymorphisms of CDKN2B, HDAC9, NINJ2, NAA25 genes.Journal of thrombosis and thrombolysis · 2019Trial
- Trial
- Protein acetylation in atherosclerosis: beyond inflammation to core cellular processes and therapeutic potential.Frontiers in immunology · 2026Review
- Genetic and epigenetic architectures of stroke: Insights from GWAS to precision medicine.Neurochemistry international · 2025Review
- Epigenetic Regulation in Ischemic Neuroprotection: The Dual Role of HDACs and HATs in Neuroinflammation and Recovery.Antioxidants (Basel, Switzerland) · 2025Review
- HDAC9 Deficiency Upregulates cGMP-dependent Kinase II to Mitigate Neuronal Apoptosis in Ischemic Stroke.Translational stroke research · 2025Article
- Unveiling the Therapeutic Promise of Epigenetics in Vascular Cognitive Impairment and Vascular Dementia.Aging and disease · 2025Review
- Indole-3-Carboxaldehyde Inhibits Inflammatory Response and Lipid Accumulation in Macrophages Through the miR-1271-5p/HDAC9 Pathway.Journal of cellular and molecular medicine · 2024Article
- Genetics of ischemic stroke functional outcome.Journal of neurology · 2024Review
- CircRNAs in Alzheimer's disease: What are the prospects?Non-coding RNA research · 2024Review
- HDAC9 as a Privileged Target: Reviewing its Role in Different Diseases and Structure-activity Relationships (SARs) of its Inhibitors.Mini reviews in medicinal chemistry · 2024Review
- Inhibition of Intimal Thickening By PRH (Proline-Rich Homeodomain) in Mice.Arteriosclerosis, thrombosis, and vascular biology · 2023Article
- Stroke by inducing HDAC9-dependent deacetylation of HIF-1 and Sp1, promotes TfR1 transcription and GPX4 reduction, thus determining ferroptotic neuronal death.International journal of biological sciences · 2023Article
- Epigenetic mechanisms and potential therapeutic targets in stroke.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2022Review
- Genetics of ANCA-associated vasculitis: role in pathogenesis, classification and management.Nature reviews. Rheumatology · 2022Review
- miR-383-5p Regulated by the Transcription Factor CTCF Affects Neuronal Impairment in Cerebral Ischemia by Mediating Deacetylase HDAC9 Activity.Molecular neurobiology · 2022Article
- Identification and functional characterization of a novel susceptibility locus for small vessel vasculitis with MPO-ANCA.Rheumatology (Oxford, England) · 2022Article
- Role of circRNA in pathogenesis of AlzheimerZhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2022Article
5 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 3 countries.
Funding
Abstract
background and purposeA novel association between a single nucleotide polymorphism on chromosome 7p21.1 and large-vessel ischemic stroke was recently identified. The most likely underlying gene is histone deacetylase 9 (HDAC9). The mechanism by which HDAC9 increases stroke risk is not clear; both vascular and neuronal mechanisms have been proposed.
methodsWe determined whether the lead single nucleotide polymorphisms were associated with asymptomatic carotid plaque (N=25 179) and carotid intima-media thickness (N=31 210) detected by carotid ultrasound in a meta-analysis of population-based and community cohorts. Immunohistochemistry was used to determine whether HDAC9 was expressed in healthy human cerebral and systemic arteries. In the Tampere Vascular Study, we determined whether HDAC9 mRNA expression was altered in carotid (N=29), abdominal aortic (N=15), and femoral (N=24) atherosclerotic plaques compared with control (left internal thoracic, N=28) arteries.
resultsBoth single nucleotide polymorphisms (rs11984041 and rs2107595) were associated with common carotid intima-media thickness (rs2107595; P=0.0018) and with presence of carotid plaque (rs2107595; P=0.0022). In both cerebral and systemic arteries, HDAC9 labeling was seen in nuclei and cytoplasm of vascular smooth muscle cells, and in endothelial cells. HDAC9 expression was upregulated in carotid plaques compared with left internal thoracic controls (P=0.00000103). It was also upregulated in aortic and femoral plaques compared with controls, with mRNA expression increased in carotid compared with femoral plaques (P=0.0038).
conclusionsOur results are consistent with the 7p21.1 association acting via promoting atherosclerosis, and consistent with alterations in HDAC9 expression mediating this increased risk. Further studies in experimental models are required to confirm this link.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.