Evidence map›Paper›PMID 23449258›Full record

ArticleStroke2013

Evidence HDAC9 genetic variant associated with ischemic stroke increases risk via promoting carotid atherosclerosis.

Hugh S Markus, Kari-Matti Mäkelä, Steve Bevan, Emma Raitoharju, Niku Oksala, Joshua C Bis, Chris O'Donnell, Atticus Hainsworth, Terho Lehtimäki

Open access · bronzeAbstract read
In one paragraph

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.

0numbers the graph read from it
0cells of the map it votes in
65citing papers in PubMed, 2 pooled it
4.6field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

65 citing papers in PubMed, 2 syntheses or guidelines pooled it, 112 citations in OpenAlex.

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  14. Inhibition of Intimal Thickening By PRH (Proline-Rich Homeodomain) in Mice.Arteriosclerosis, thrombosis, and vascular biology · 2023
    Article
  15. Article
  16. 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 · 2022
    Review
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  18. Article
  19. Article
  20. Role of circRNA in pathogenesis of AlzheimerZhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2022
    Article

5 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 3 institutions in 3 countries.

Hugh S MarkusStroke and Dementia Research Centre, St George's University of London, London SW19 3QZ, United Kingdom. hmarkus@sgul.ac.uk
Kari-Matti Mäkelä
Steve Bevan
Emma Raitoharju
Niku Oksala
Joshua C Bis
Chris O'Donnell
Atticus Hainsworth
Terho Lehtimäki
Tampere University · FISt George's, University of London · GBTampere University Hospital · FI

Funding

Genomic Epidemiology of Cardiovascular DiseaseZIAHL006002 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI O'DONNELL, CHRISTOPHER · 2009 to 2015
$8.0M
Gene Expression for Functional Genomics in Human PopulationsZIAHL006175 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI O'DONNELL, CHRISTOPHER · 2013 to 2015
$2.2M
Functional Genetic Variation Underlying Cardiovascular Genomic EpidemiologyZIAHL006173 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI O'DONNELL, CHRISTOPHER · 2013 to 2015
$2.0M
Intramural NIH HHS Z99 HL999999Intramural NIH HHS ZIA HL006002
6 · The paper itself

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.

Indexed as

Genetic Predisposition to DiseasePolymorphism, Single NucleotideAdultAgedAged, 80 and overAortaAtherosclerosisBrain IschemiaCarotid ArteriesCarotid Artery DiseasesCarotid Intima-Media ThicknessFemaleHistone DeacetylasesHumansMaleMiddle AgedHDAC9 protein, humanHistone DeacetylasesRepressor Proteins

Identifiers

PMID23449258
PMCPMC4206941
OpenAlexW2155650206

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.