Palmirotta Raffaele, Barbanti Piero, De Marchis Maria Laura, Egeo Gabriella, Aurilia Cinzia, Fofi Luisa, Ialongo Cristiano, Valente Maria Giovanna, Ferroni Patrizia, Della-Morte David, Guadagni Fiorella
1 Interinstitutional Multidisciplinary Biobank (BioBIM), Biomarker Discovery and Advanced Technologies (BioDAT), IRCCS San Raffaele Pisana , Rome, Italy .
Antioxid Redox Signal. 2015 Jan 20;22(3):275-9. doi: 10.1089/ars.2014.6069. Epub 2014 Nov 11.
Several studies suggest a role of oxidative stress in the physiopathology of migraine, particularly in the form with aura. In a case-control study, we investigated the association between migraine and superoxide dismutase 1 (SOD1) and superoxide dismutase 2 (SOD2) genes in a cohort of 490 consecutive unrelated Caucasian migraineurs (migraine with aura [MwA], n=107; migraine without aura [MwoA], n=246; chronic migraine [CM], n=137) and 246 healthy controls recruited at our Headache and Pain Unit and stored in the Interinstitutional Multidisciplinary BioBank (BioBIM). Migraine phenotype was carefully detailed using face-to-face interviews. We examined polymorphisms of SOD1 gene (A/C substitution-rs2234694) and SOD2 gene (C/T transition-rs4880-Ala16Val). The rs4880 TT (Val/Val) genotype was associated (p=0.042) with the presence of unilateral cranial autonomic symptoms (UAs) in MwA patients. We also found a mild correlation between SOD2 rs4880 genotype and the type of acute migraine treatment (p=0.048) in MwA patients. Our findings suggest that SOD2 is a disease-modifier gene influencing oxidative mechanisms in MwA. These observations lead to the hypothesis that SOD2 polymorphism may cause a defective control of the oxidative phenomena linked to cortical spreading depression, the neurophysiological hallmark of migraine aura, causing an overstimulation of trigeminal neurons and UAs triggering.
多项研究表明氧化应激在偏头痛的病理生理过程中发挥作用，尤其是有先兆的偏头痛。在一项病例对照研究中，我们调查了490名连续入选的无亲缘关系的白种人偏头痛患者（有先兆偏头痛[MwA]，n = 107；无先兆偏头痛[MwoA]，n = 246；慢性偏头痛[CM]，n = 137）以及在我们头痛与疼痛科招募并存储于机构间多学科生物样本库（BioBIM）中的246名健康对照者中偏头痛与超氧化物歧化酶1（SOD1）和超氧化物歧化酶2（SOD2）基因之间的关联。通过面对面访谈仔细详细描述偏头痛表型。我们检测了SOD1基因（A/C替换 - rs2234694）和SOD2基因（C/T转换 - rs4880 - Ala16Val）的多态性。rs4880 TT（Val/Val）基因型与MwA患者单侧颅自主神经症状（UAs）的存在相关（p = 0.042）。我们还发现MwA患者中SOD2 rs4880基因型与急性偏头痛治疗类型之间存在轻度相关性（p = 0.048）。我们的研究结果表明SOD2是影响MwA氧化机制的疾病修饰基因。这些观察结果引出一个假设，即SOD2多态性可能导致与皮质扩散性抑制相关的氧化现象控制缺陷，皮质扩散性抑制是偏头痛先兆的神经生理学标志，导致三叉神经神经元过度刺激和UAs触发。
