Global DNA methylation of ischemic stroke subtypes.
Ischemic stroke (IS), a heterogeneous multifactorial disorder, is among the leading causes of mortality and long-term disability in the western world. Epidemiological data provides evidence for a genetic component to the disease, but its epigenetic involvement is still largely unknown. Epigenetic mechanisms, such as DNA methylation, change over time and may be associated with aging processes and with modulation of the risk of various pathologies, such as cardiovascular disease and stroke. We analyzed 2 independent cohorts of IS patients. Global DNA methylation was measured by luminometric methylation assay (LUMA) of DNA blood samples. Univariate and multivariate regression analyses were used to assess the methylation differences between the 3 most common IS subtypes, large-artery atherosclerosis (LAA), small-artery disease (SAD), and cardio-aortic embolism (CE). A total of 485 IS patients from 2 independent hospital cohorts (n = 281 and n = 204) were included, distributed across 3 IS subtypes: LAA (78/281, 59/204), SAD (97/281, 53/204), and CE (106/281, 89/204). In univariate analyses, no statistical differences in LUMA levels were observed between the 3 etiologies in either cohort. Multivariate analysis, adjusted by age, sex, hyperlipidemia, and smoking habit, confirmed the lack of differences in methylation levels between the analyzed IS subtypes in both cohorts. Despite differences in pathogenesis, our results showed no global methylation differences between LAA, SAD, and CE subtypes of IS. Further work is required to establish whether the epigenetic mechanism of methylation might play a role in this complex disease.
Department of Neurology, Neurovascular Research Group, IMIM-Hospital del Mar (Institut Hospital del Mar d'Investigacions Mèdiques), Universitat Autonoma de Barcelona/DCEXS-Universitat Pompeu Fabra, Barcelona, Spain.
Carolina
C
Soriano-Tárraga
Department of Neurology, Neurovascular Research Group, IMIM-Hospital del Mar (Institut Hospital del Mar d'Investigacions Mèdiques), Universitat Autonoma de Barcelona/DCEXS-Universitat Pompeu Fabra, Barcelona, Spain.
Jordi
J
Jiménez-Conde
Department of Neurology, Neurovascular Research Group, IMIM-Hospital del Mar (Institut Hospital del Mar d'Investigacions Mèdiques), Universitat Autonoma de Barcelona/DCEXS-Universitat Pompeu Fabra, Barcelona, Spain.
Eva
E
Giralt-Steinhauer
Department of Neurology, Neurovascular Research Group, IMIM-Hospital del Mar (Institut Hospital del Mar d'Investigacions Mèdiques), Universitat Autonoma de Barcelona/DCEXS-Universitat Pompeu Fabra, Barcelona, Spain.
Marina
M
Mola
Department of Neurology, Neurovascular Research Group, IMIM-Hospital del Mar (Institut Hospital del Mar d'Investigacions Mèdiques), Universitat Autonoma de Barcelona/DCEXS-Universitat Pompeu Fabra, Barcelona, Spain.
Angel
A
Ois
Department of Neurology, Neurovascular Research Group, IMIM-Hospital del Mar (Institut Hospital del Mar d'Investigacions Mèdiques), Universitat Autonoma de Barcelona/DCEXS-Universitat Pompeu Fabra, Barcelona, Spain.
Ana
A
Rodríguez-Campello
Department of Neurology, Neurovascular Research Group, IMIM-Hospital del Mar (Institut Hospital del Mar d'Investigacions Mèdiques), Universitat Autonoma de Barcelona/DCEXS-Universitat Pompeu Fabra, Barcelona, Spain.
Elisa
E
Cuadrado-Godia
Laboratory of neurovascular pharmacogenomics and genetics, Fundació per la Docència i Recerca Mutua Terrassa, Terrassa (Barcelona), Spain; Neurovascular Research Laboratory, Institut de Recerca, Universitat Autònoma de Barcelona, Hospital Vall d'Hebron, Barcelona, Spain.
Israel
I
Fernández-Cadenas
Neurovascular Research Laboratory, Institut de Recerca, Universitat Autònoma de Barcelona, Hospital Vall d'Hebron, Barcelona, Spain.
Caty
C
Carrera
Neurovascular Research Laboratory, Institut de Recerca, Universitat Autònoma de Barcelona, Hospital Vall d'Hebron, Barcelona, Spain.
Joan
J
Montaner
Cardiovascular Epidemiology and Genetics group, Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), Barcelona, Spain.
Roberto
R
Elosua
Department of Neurology, Neurovascular Research Group, IMIM-Hospital del Mar (Institut Hospital del Mar d'Investigacions Mèdiques), Universitat Autonoma de Barcelona/DCEXS-Universitat Pompeu Fabra, Barcelona, Spain.
Jaume
J
Roquer
D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D004247:DNA / Q000097:blood / Q000235:genetics; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020521:Stroke / Q000097:blood / Q000235:genetics*
D004247:DNA