Page 76

Karger_ESC London_2013

22. European Stroke Conference Figure 1: Mean levels of global DNA methylation with 95%CI in DNA pools from stroke sub-types and controls 16 Etiology of stroke and risk factors B 17:30 - 17:40 Epigenome wide analysis of methylation profiles using DNA pools shows differences ac-cording to stroke subtype. M.J. Macleod1, O. Pogoryelova2, G. Horgan3, P. Haggarty4 University of Aberdeen, Aberdeen, UNITED KINGDOM1,university of Aberdeen, Aber-deen, UNITED KINGDOM2, University of Aberdeen, Aberdeen, UNITED KINGDOM3, Uni-versity of Aberdeen, Aberdeen, UNITED KINGDOM4 Background Epigenetic mechanisms, such as DNA methylation, regulate tissue specific gene expression. Environmental and lifestyle influences can lead to changes in the epigenome which may alter susceptibility to disease. Epigenetic dysregulation has been implicated in vascular disease. We hypothesised that ischemic stroke or specific subtypes might be associated with distinct leuko-cyte DNA methylation profiles compared to a control population. Methods Lymphocyte DNA from male patients was pooled according to stroke subtype: large vessel (LVD), small vessel (SVD) and cardioembolic (CE) stroke. An age matched control group was also investigated. Analysis was performed in triplicate. An epigenome-wide study (EWAS) of 485 000 methylation sites was performed using the Ifinium Illumina chip. EWAS data analysis was based on average methylation of individual CpG islands in each replication and functional groups within each gene region of interest. SPSS was used for data analysis. Results A typical biphasic distribution of methylation was observed across the genome in all analysed DNA pools. Global genome methylation was lower in CE stroke (-0.009, p<0.001), and higher in LVD stroke patients (+0.003, p<0.01) than controls. On all chromosomes, the LVD pool had higher methylation compared to control, while the CE pool had lower methylation levels except for Chromosome X. In the SVD pool either no differ-ence (Chr 3 and 4) or minor differences only were observed. Conclusion This initial exploratory study suggests differences in methylation patterns between patients with different stroke aetiologies (large vessel disease, small vessel disease and cardioembolic stroke), and from a non-stroke population. While cause and effect is unclear, it may suggest that alterations in methylation either predispose to stroke, or arise as a result of vessel changes or chronic disease states. The data is preliminary and requires to be replicated and confirmed in in-dividual samples. 76 © 2013 S. Karger AG, Basel Scientific Programme


Karger_ESC London_2013
To see the actual publication please follow the link above