DNA Hypomethylation of the MPO Gene in Peripheral Blood Leukocytes Is Associated with Cerebral Stroke in the Acute Phase.

Autor: Bushueva O; Research Institute for Genetic and Molecular Epidemiology, Kursk State Medical University, Kursk, Russia. olga.bushueva@inbox.ru.; Department of Biology, Medical Genetics and Ecology, Kursk State Medical University, Kursk, Russia. olga.bushueva@inbox.ru., Barysheva E; Department of Biology, Medical Genetics and Ecology, Kursk State Medical University, Kursk, Russia., Markov A; Research Institute of Medical Genetics, Tomsk National Research Medical Center, Russian Academy of Sciences, Tomsk, Russia., Belykh A; Department of Pathophysiology, Kursk State Medical University, Kursk, Russia., Koroleva I; Research Institute of Medical Genetics, Tomsk National Research Medical Center, Russian Academy of Sciences, Tomsk, Russia., Churkin E; Research Institute of Medical Genetics, Tomsk National Research Medical Center, Russian Academy of Sciences, Tomsk, Russia., Polonikov A; Research Institute for Genetic and Molecular Epidemiology, Kursk State Medical University, Kursk, Russia.; Department of Biology, Medical Genetics and Ecology, Kursk State Medical University, Kursk, Russia., Ivanov V; Department of Biology, Medical Genetics and Ecology, Kursk State Medical University, Kursk, Russia., Nazarenko M; Research Institute of Medical Genetics, Tomsk National Research Medical Center, Russian Academy of Sciences, Tomsk, Russia.
Jazyk: angličtina
Zdroj: Journal of molecular neuroscience : MN [J Mol Neurosci] 2021 Sep; Vol. 71 (9), pp. 1914-1932. Date of Electronic Publication: 2021 Apr 17.
DOI: 10.1007/s12031-021-01840-8
Abstrakt: Dysregulation of the oxidant-antioxidant system contributes to the pathogenesis of cerebral stroke (CS). Epigenetic changes of redox homeostasis genes, such as glutamate-cysteine ligase (GCLM), glutathione-S-transferase-P1 (GSTP1), thioredoxin reductase 1 (TXNRD1), and myeloperoxidase (MPO), may be biomarkers of CS. In this study, we assessed the association of DNA methylation levels of these genes with CS and clinical features of CS. We quantitatively analyzed DNA methylation patterns in the promoter or regulatory regions of 4 genes (GCLM, GSTP1, TXNRD1, and MPO) in peripheral blood leukocytes of 59 patients with CS in the acute phase and in 83 relatively healthy individuals (controls) without cardiovascular and cerebrovascular diseases. We found that in both groups, the methylation level of CpG sites in genes TXNRD1 and GSTP1 was ≤ 5%. Lower methylation levels were registered at a CpG site (chr1:94,374,293, GRCh37 [hg19]) in GCLM in patients with ischemic stroke compared with the control group (9% [7%; 11.6%] (median and interquartile range) versus 14.7% [10.4%; 23%], respectively, p < 0.05). In the leukocytes of patients with CS, the methylation level of CpG sites in the analyzed region of MPO (chr17:56,356,470, GRCh3 [hg19]) on average was significantly lower (23.5% [19.3%; 26.7%]) than that in the control group (35.6% [30.4%; 42.6%], p < 0.05). We also found increased methylation of MPO in smokers with CS (27.2% [23.5%; 31.1%]) compared with nonsmokers with CS (21.7% [18.1%; 24.8%]). Thus, hypomethylation of CpG sites in GCLM and MPO in blood leukocytes is associated with CS in the acute phase.
(© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
Databáze: MEDLINE
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