Dias Andreia, Ferreira Marta, Santos Mariana, Sousa Alda, Oliveira Carla, Alves-Ferreira Miguel, Lemos Carolina
i3S-Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto 4200-135, Portugal.
Unidade Multidisciplinar de Investigação Biomédica (UMIB), Instituto de Ciências Biomédicas Abel Salazar (ICBAS), Universidade do Porto, Porto 4050-313, Portugal.
Brain Commun. 2025 Apr 28;7(2):fcaf142. doi: 10.1093/braincomms/fcaf142. eCollection 2025.
Migraine is a complex neurological disorder, and the most common migraine categories are migraine with aura and without aura. The higher prevalence of migraine in related individuals compared to the general population indicates a potential genetic predisposition; however, gene expression, which is influenced by both genetic and environmental factors, can also be a major factor in the migraine susceptibility. Given the high number of Portuguese migraine patients whose diagnosis and treatment have not yet been well established, we decided to carry out a whole transcriptome analysis within a migraine Portuguese cohort. This study aims to identify potential biomarkers that could contribute to improved migraine therapy. We performed total RNA sequencing on whole blood samples from 15 migraine patients and 12 age-matched controls. Differential expression analysis and gene set enrichment analysis were performed in different migraine subgroups. Finally, we performed the protein-protein interaction networks of differentially expressed genes. Gene set enrichment analysis comparing migraine patients with controls highlighted upregulated pathways linked to metabolism, and downregulated immuno-inflammatory pathways. Moreover, the groups of female migraine patients and female migraine without aura patients emphasized significant upregulated pathways, including G protein-coupled receptors signalling pathways, when compared with female controls. Interestingly, we found two important differentially expressed genes related to parathyroid hormone: and . was upregulated in female migraine without aura versus female controls, while was both upregulated between female migraine patients and female controls, as well as between female migraine without aura and controls. Here, we show, for the first time, the involvement of parathyroid hormone receptors and their associated gene expression patterns in female migraine patients. These molecules stand out as sturdy and promising biomarkers for innovative therapeutic in female migraine patients.
偏头痛是一种复杂的神经系统疾病，最常见的偏头痛类型是有先兆偏头痛和无先兆偏头痛。与普通人群相比，偏头痛在相关个体中的患病率更高，这表明存在潜在的遗传易感性；然而，受遗传和环境因素影响的基因表达也可能是偏头痛易感性的主要因素。鉴于大量葡萄牙偏头痛患者的诊断和治疗尚未得到很好的确立，我们决定在一个葡萄牙偏头痛队列中进行全转录组分析。本研究旨在识别可能有助于改善偏头痛治疗的潜在生物标志物。我们对15名偏头痛患者和12名年龄匹配的对照的全血样本进行了全RNA测序。在不同的偏头痛亚组中进行了差异表达分析和基因集富集分析。最后，我们构建了差异表达基因的蛋白质-蛋白质相互作用网络。比较偏头痛患者和对照的基因集富集分析突出显示了与代谢相关的上调途径和免疫炎症途径的下调。此外，与女性对照相比，女性偏头痛患者组和无先兆女性偏头痛患者组强调了显著上调的途径，包括G蛋白偶联受体信号通路。有趣的是，我们发现了两个与甲状旁腺激素相关的重要差异表达基因： 和 。 在无先兆女性偏头痛患者与女性对照相比中上调，而 在女性偏头痛患者与女性对照之间以及无先兆女性偏头痛患者与对照之间均上调。在这里，我们首次展示了甲状旁腺激素受体及其相关基因表达模式在女性偏头痛患者中的作用。这些分子作为女性偏头痛患者创新治疗的强大且有前景的生物标志物脱颖而出。
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