Carvalho Estefânia, Dias Andreia, Sousa Alda, Lopes Alexandra M, Martins Sandra, Pinto Nádia, Lemos Carolina, Alves-Ferreira Miguel
Instituto de Investigação e Inovação em Saúde (i3S), Universidade do Porto, 4200-135 Porto, Portugal.
Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), 4200-135 Porto, Portugal.
Brain Sci. 2022 Apr 21;12(5):526. doi: 10.3390/brainsci12050526.
Migraine is a complex neurovascular disorder affecting one billion people worldwide, mainly females. It is characterized by attacks of moderate to severe headache pain, with associated symptoms. Receptor activity modifying protein (RAMP1) is part of the Calcitonin Gene-Related Peptide (CGRP) receptor, a pharmacological target for migraine. Epigenetic processes, such as DNA methylation, play a role in clinical presentation of various diseases. DNA methylation occurs mostly in the gene promoter and can control gene expression. We investigated the methylation state of the promoter in 104 female blood DNA samples: 54 migraineurs and 50 controls. We treated DNA with sodium bisulfite and performed PCR, Sanger Sequencing, and Epigenetic Sequencing Methylation (ESME) software analysis. We identified 51 CpG dinucleotides, and 5 showed methylation variability. Migraineurs had a higher number of individuals with all five CpG methylated when compared to controls (26% vs. 16%), although non-significant ( = 0.216). We also found that CpG -284 bp, related to the transcription start site (TSS), showed higher methylation levels in cases ( = 0.011). This CpG may potentially play a role in migraine, affecting transcription or receptor malfunctioning and/or altered CGRP binding. We hope to confirm this finding in a larger cohort and establish an epigenetic biomarker to predict female migraine risk.
偏头痛是一种复杂的神经血管疾病，全球有10亿人受其影响，主要为女性。其特征是发作性中度至重度头痛，并伴有相关症状。受体活性调节蛋白1（RAMP1）是降钙素基因相关肽（CGRP）受体的一部分，而CGRP受体是偏头痛的一个药物靶点。表观遗传过程，如DNA甲基化，在各种疾病的临床表现中起作用。DNA甲基化主要发生在基因启动子区域，并可控制基因表达。我们研究了104份女性血液DNA样本（54名偏头痛患者和50名对照）中该启动子的甲基化状态。我们用亚硫酸氢钠处理DNA，并进行了聚合酶链反应（PCR）、桑格测序以及表观遗传测序甲基化（ESME）软件分析。我们鉴定出51个CpG二核苷酸，其中5个显示出甲基化变异性。与对照组相比，偏头痛患者中所有五个CpG均甲基化的个体数量更多（26%对16%），尽管差异不显著（P = 0.216）。我们还发现，与转录起始位点（TSS）相关的CpG -284 bp在病例组中显示出更高的甲基化水平（P = 0.011）。这个CpG可能在偏头痛中发挥作用，影响转录或受体功能异常和/或改变CGRP结合。我们希望在更大的队列中证实这一发现，并建立一种表观遗传生物标志物来预测女性偏头痛风险。
