Obesity and ischemic stroke modulate the methylation levels of KCNQ1 in white blood cells
Ana M. Gómez-Úriz,Fermín I. Milagro,Fermín I. Milagro,Maria L. Mansego,Paul Cordero,Itziar Abete,Ana de Arce,Estibaliz Goyenechea,Vanessa Blázquez,Maite Martínez-Zabaleta,J. A. Martínez,Adolfo López de Munain,Javier Campión +12 more
TL;DR: Obesity induced changes in the KCNQ1 methylation pattern which were also dependent on stroke, and these DNA methylation patterns could be used as future potential stroke biomarkers.
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Abstract: Obesity and stroke are multifactorial diseases in which genetic, epigenetic and lifestyle factors are involved. The research aims were, first, the description of genes with differential epigenetic regulation obtained by an 'omics' approach in patients with ischemic stroke and, second, to determine the importance of some regions of these selected genes in biological processes depending on the body mass index. A case-control study using two populations was designed. The first population consisted of 24 volunteers according to stroke/non-stroke and normal weight/obesity conditions. The second population included 60 stroke patients and 55 controls classified by adiposity. DNA from the first population was analyzed with a methylation microarray, showing 80 cytosine-guanine dinucleotides (CpG) sites differentially methylated in stroke and 96 CpGs in obesity, whereas 59 CpGs showed interaction. After validating these data by MassArray Epityper, the promoter region of peptidase M20 domain containing 1 (PM20D1) gene was significantly hypermethylated in stroke patients. One CpG site at Caldesmon 1 (CALD1) gene showed an interaction between stroke and obesity. Two CpGs located in the genes Wilms' tumor 1 (WT1) and potassium voltage-gated channel, KQT-like subfamily, member 1 (KCNQ1) were significantly hypermethylated in obese patients. In the second population, KCNQ1 was also hypermethylated in the obese subjects. Two CpGs of this gene were subsequently validated by methylation-sensitive high-resolution melting. Moreover, KCNQ1 methylation levels were associated with plasma KCNQ1 protein concentrations. In conclusion, obesity induced changes in the KCNQ1 methylation pattern which were also dependent on stroke. Furthermore, the epigenetic marks differentially methylated in the stroke patients were dependent on the previous obese state. These DNA methylation patterns could be used as future potential stroke biomarkers.
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Multi-omics research strategies in ischemic stroke: A multidimensional perspective
TL;DR: In this article , the authors consider advances in genomics, transcriptomics, proteomics and metabolomics and outline their use in discovering the biomarkers and pathological mechanisms of stroke and discuss strategies for achieving integration at the multi-omics level and discuss how integrative omics and systems biology can contribute to our understanding and management of stroke.
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Multivariate analysis of genome-wide data to identify potential pleiotropic genes for type 2 diabetes, obesity and coronary artery disease using MetaCCA
Xiaocan Jia,Yongli Yang,Yuan-Cheng Chen,Zhenhua Xia,Weiping Zhang,Yu Feng,Yifan Li,Jiebing Tan,Chao Xu,Qiang Zhang,Hong-Wen Deng,Xuezhong Shi +11 more
TL;DR: The metaCCA method identified novel variants associated with T2D, obesity and CAD by effectively incorporating information from different GWAS datasets and may provide insights for some common therapeutic approaches of metabolic diseases based on the pleiotropic genes and common mechanisms identified.
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The Role of DNA Methylation in Ischemic Stroke: A Systematic Review.
Minyan Zeng,Juanying Zhen,Juanying Zhen,Xiaodan Zheng,Xiaodan Zheng,Hongyan Qiu,Xiaonan Xu,Jun Wu,Zhijian Lin,Jun Hu +9 more
TL;DR: DNA methylation might be associated with ischemic stroke and play a role in several pathological pathways, but the current evidence is limited by sample size and cross-sectional or retrospective design, therefore, studies on large asymptomatic populations with the prospective design are needed.
Examining the association between adiposity and DNA methylation: A systematic review and meta-analysis
Whitney L Do,Jazib Gohar,Lauren E. McCullough,Karla I. Galaviz,Karen N. Conneely,K.M. Venkat Narayan +5 more
TL;DR: In this paper, the authors show that DNA methylation at 52 CpG sites represent potential mediators of obesity-associated chronic diseases and may be novel intervention or therapeutic targets to protect against obesity associated chronic diseases such as type 2 diabetes, cardiovascular disease, Crohn's disease, and depression.
21
Thinking outside the Ischemia Box: Advancements in the Use of Multiple Sclerosis Drugs in Ischemic Stroke.
Athina-Maria Aloizou,Vasileios Siokas,Georgia Pateraki,Ioannis Liampas,Christos Bakirtzis,Zisis Tsouris,George Lazopoulos,Daniela Calina,Anca Oana Docea,Aristidis Tsatsakis,Dimitrios P. Bogdanos,Efthimios Dardiotis +11 more
TL;DR: In this article, the authors present a review of the available studies and discuss their potential in ameliorating the outcomes of Ischemic stroke (IS) in the setting of MS.
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