DNA methylation analyses identify an intronic ZDHHC6 locus associated with time to recurrent stroke in the Vitamin Intervention for Stroke Prevention (VISP) clinical trial
Davis Armstrong, N.M. (East Carolina University. Department of Biology)
Chen, Wei-Min (University of Virginia. Department of Public Health Sciences)
Hsu, F.C. (Wake Forest School of Medicine)
Brewer, M.S. (East Carolina University. Department of Biology)
Cullell, Natalia (Fundació per la Recerca Biomèdica i Social Mútua de Terrassa)
Fernandez-Cadenas, Israel (Institut d'Investigació Biomèdica Sant Pau)
Williams, S.R. (University of Virginia. Department of Neurology)
Sale, M.M. (University of Virginia. Department of Public Health Sciences)
Worrall, B.B. (University of Virginia. Department of Neurology)
Keene, K.L. (East Carolina University. Brody School of Medicine)

Fecha:	2021
Resumen:	Aberrant DNA methylation profiles have been implicated in numerous cardiovascular diseases; however, few studies have investigated how these epigenetic modifications contribute to stroke recurrence. The aim of this study was to identify methylation loci associated with the time to recurrent cerebro- and cardiovascular events in individuals of European and African descent. DNA methylation profiles were generated for 180 individuals from the Vitamin Intervention for Stroke Prevention clinical trial using Illumina HumanMethylation 450K BeadChip microarrays, resulting in beta values for 470,871 autosomal CpG sites. Ethnicity-stratified survival analyses were performed using Cox Proportional Hazards regression models for associations between each methylation locus and the time to recurrent stroke or composite vascular event. Results were validated in the Vall d'Hebron University Hospital cohort from Barcelona, Spain. Network analyses of the methylation loci were generated using weighted gene coexpression network analysis. Primary analysis identified four significant loci, cg04059318, ch. 2. 81927627R, cg03584380, and cg24875416, associated with time to recurrent stroke. Secondary analysis identified three loci, cg00076998, cg16758041, and cg02365967, associated with time to composite vascular endpoint. Locus cg03584380, which is located in an intron of ZDHHC6, was replicated in the Vall d'Hebron University Hospital cohort. The results from this study implicate the degree of methylation at cg03584380 is associated with the time of recurrence for stroke or composite vascular events across two ethnically diverse groups. Furthermore, modules of loci were associated with clinical traits and blood biomarkers including previous number of strokes, prothrombin fragments 1 + 2, thrombomodulin, thrombin-antithrombin complex, triglyceride levels, and tissue plasminogen activator. Ultimately, these loci could serve as potential epigenetic biomarkers that could identify at-risk individuals in recurrence-prone populations.
Nota:	Altres ajuts: National Institutes of Health (grant U01HG005160); National Human Genome Research Institute (Supplement U01HG005160-03S1); American Heart Association Scientist Development Award (12SDG9180012); Faith Christian Center International (Charlottesville, VA). National Institute of Neurological Disorders and Stroke (R01 NS34447).
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	Acyltransferases ; Aged ; DNA Methylation ; Epigenome ; Female ; Humans ; Male ; Middle Aged ; Stroke ; Vitamins
Publicado en:	PloS one, Vol. 16 Núm. 7 July (july 2021) , p. e0254562, ISSN 1932-6203

DOI: 10.1371/journal.pone.0254562
PMID: 34252155

17 p, 2.6 MB

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