METHYLATION BIOMARKERS ASSOCIATED WITH DRUG-RESISTANT EPILEPSY
METHYLATION BIOMARKERS ASSOCIATED WITH DRUG-RESISTANT EPILEPSY
ABSTRACT Epilepsy is a disabling neurological disease that affects 2% of the population. Drug-resistant epilepsy (DRE) affects 25-30% of epilepsy patients. Understanding its underlying mechanisms is key to adequately manage this condition. To analyze the main epigenetic marks of DRE an epigenome-wide association study was carried out including samples from different regions of DRE patients’ brain and peripheral blood. An Illumina Infinium MethylationEPIC BeadChip array including cortex, hippocampus, amygdala, and peripheral blood from DRE subjected to neurosurgical resection of the epileptogenic zone was used. Overall, 32, 59, 3210, and 6 differentially methylated probes (DMPs) associated with DRE were found in the hippocampus, amygdala, cortex, and peripheral blood, respectively. These DMPs harbored 19, 28, 1574, and 7 genes, respectively, which play different roles in processes such as neurotrophic or calcium signaling. Three of the top DMPs observed in cortex were validated with methylation specific qPCR. Moreover, 163 DMPs associated with neurosurgery response at 6 months were found in the hippocampus. Genes located on these DMPs were involved in diverse processes such as synaptic signaling and central nervous system development. Besides 3 DMPs in blood samples were associated with response to neurosurgery at 12 months. In conclusion, the present study reports genome-wide DNA methylation changes across different regions of the DRE brain. These changes could be useful for further studies to disentangle the bases of DRE to search for therapeutic alternatives for this disease. Furthermore, they could also help identify patients likely to respond to neurosurgery.
Nava-Cede?o Desir¨|e、Ovejero-Benito Mar¨aa Carmen、Navas Marta、De Toledo Mar¨aa、Granero-Cremades Inmaculada、Pulido Paloma、Abad-Santos Francisco、Gago-Veiga Ana Beatriz、Alonso-Cerezo Mar¨aa Concepci¨?n、Elizalde-Horcada Marcos、Alonso-Guirado Lola、S¨￠nchez Jim¨|nez Patricia、Sanz-Garc¨aa Ancor、Torres-D¨aaz Cristina Virginia
Department of Clinical Genetics. Hospital Universitario de la PrincesaDepartment of Clinical Pharmacology, Universidad Aut¨?noma de Madrid, Hospital Universitario de La Princesa, Instituto de Investigaciones Sanitarias La Princesa (IIS-Princesa)||Departamento de Ciencias Farmac¨|uticas y de la Salud, Facultad de Farmacia, Universidad San Pablo-CEU, CEU UniversitiesDepartment of Neurosurgery, Hospital Universitario de La PrincesaDepartment of Neurology, Hospital Universitario de La PrincesaDepartment of Clinical Analysis. Hospital Universitario de la PrincesaDepartment of Neurosurgery, Hospital Universitario de La PrincesaDepartment of Clinical Pharmacology, Universidad Aut¨?noma de Madrid, Hospital Universitario de La Princesa, Instituto de Investigaciones Sanitarias La Princesa (IIS-Princesa)||Centro de Investigaci¨?n Biom¨|dica en Red de Enfermedades Hep¨￠ticas y Digestivas (CIBERehd), Instituto de Salud Carlos IIIDepartment of Neurology, Hospital Universitario de La PrincesaDepartment of Clinical Genetics. Hospital Universitario de la PrincesaDepartment of Clinical Pharmacology, Universidad Aut¨?noma de Madrid, Hospital Universitario de La Princesa, Instituto de Investigaciones Sanitarias La Princesa (IIS-Princesa)||Unidad de Bioinform¨￠tica, Plataforma de apoyo a la investigaci¨?n, Instituto de Investigaciones Sanitarias Pere Virgili (ISS-PV)Genetic & Molecular Epidemiology Group, Spanish National Cancer Research Center (CNIO)Department of Clinical Pharmacology, Universidad Aut¨?noma de Madrid, Hospital Universitario de La Princesa, Instituto de Investigaciones Sanitarias La Princesa (IIS-Princesa)||NIMGenetics Gen¨?mica y Medicina S.L.Data Analysis Unit, Hospital Universitario de la Princesa, Instituto de Investigaci¨?n Sanitaria La Princesa (IIS-IP)Department of Neurosurgery, Hospital Universitario de La Princesa
神经病学、精神病学基础医学生物科学研究方法、生物科学研究技术
DNA methylation arraydrug-resistant epilepsy (DRE)epigenome-wide association array (EWAS)epilepsy biomarkersepigenetics
Nava-Cede?o Desir¨|e,Ovejero-Benito Mar¨aa Carmen,Navas Marta,De Toledo Mar¨aa,Granero-Cremades Inmaculada,Pulido Paloma,Abad-Santos Francisco,Gago-Veiga Ana Beatriz,Alonso-Cerezo Mar¨aa Concepci¨?n,Elizalde-Horcada Marcos,Alonso-Guirado Lola,S¨￠nchez Jim¨|nez Patricia,Sanz-Garc¨aa Ancor,Torres-D¨aaz Cristina Virginia.METHYLATION BIOMARKERS ASSOCIATED WITH DRUG-RESISTANT EPILEPSY[EB/OL].(2025-03-28)[2025-07-22].https://www.medrxiv.org/content/10.1101/2022.03.14.22271975.点此复制
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