Background Migraine is a polygenetic disease, considered as a channelopathy. The dysregulation of ion functioning due to genetic changes may activate the trigeminovascular system and induce migraine attack both migraine with aura (MA) and without aura (MO). Objectives The aim of the study was to analyze the following variants of genes encoding ion channels and associated protein: c.3199G>A SCN1A, c.56G>A SCN2A, c.28A>G and c.328T>C KCNK18, c.3053A>G TRPA1, c.31-1811C>T STX1A in migraine patients. Patients and Methods The study included 170 migraine patients and 173 controls. HRMA and Sanger sequencing were used for genotyping. Meta-analysis was performed for c.28A>G, c.328T>C KCNK18, and c.31-1811C>T STX1A. Results AA genotype of c.56G>A SCN2A was found only in migraine patients. Patients with c.328T>C KCNK18 mutation had an increased risk of developing migraine before the age of 18. Moreover, individuals with AA/TC haplotype of KCNK18 had higher attack frequency than those with AA/TT (p<0.05). T allele of c.31-1811C>T STX1A was more frequent in MA patients than MO (p<0.05). The c.3053A>G TRPA1 polymorphism was more common in patients with migraine onset before the age of 15 (p<0.05), while c.31-1811C>T STX1A and c.3199G>A SCN1A before the age of 10 (p<0.01). Meta-analysis showed a significant association of c.31-1811C>T STX1A polymorphism with migraine overall (OR=1.22, p=0.0086), MA, and MO. No association was found for c.28A>G KCNK18, c.328T>C KCNK18, and migraine overall. Conclusion Changes in genes encoding ion channels or proteins regulating their functioning may increase the risk of migraines and correlate with clinical features of disease, e.g. age of onset and attack frequency.

中文翻译：

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分析 SCN1A、SCN2A、KCNK18、TRPA1 和 STX1A 中的遗传变异作为偏头痛的可能标志物

背景偏头痛是一种多基因疾病，被认为是一种离子通道病。由于遗传变化导致的离子功能失调可能会激活三叉神经血管系统并诱发有先兆偏头痛（MA）和无先兆偏头痛（MO）的偏头痛发作。目的 本研究的目的是分析以下编码离子通道和相关蛋白的基因变异：c.3199G>A SCN1A，c.56G>A SCN2A，c.28A>G 和 c.328T>C KCNK18，c。 3053A>G TRPA1, c.31-1811C>T STX1A 在偏头痛患者中。患者和方法 该研究包括 170 名偏头痛患者和 173 名对照。HRMA 和 Sanger 测序用于基因分型。对 c.28A>G、c.328T>C KCNK18 和 c.31-1811C>T STX1A 进行了 Meta 分析。结果 AA基因型c.56G>A SCN2A仅见于偏头痛患者。c.328T患者> C KCNK18 突变在 18 岁之前发生偏头痛的风险增加。此外，具有 AA/TC 单倍型 KCNK18 的个体比具有 AA/TT 的个体具有更高的发作频率（p<0.05）。c.31-1811C>T STX1A 的 T 等位基因在 MA 患者中比在 MO 患者中更常见（p<0.05）。c.3053A>G TRPA1 多态性在 15 岁之前偏头痛发作的患者中更常见（p<0.05），而 c.31-1811C>T STX1A 和 c.3199G>A SCN1A 在 10 岁之前更常见（p <0.01)。Meta 分析显示 c.31-1811C>T STX1A 多态性与总体偏头痛（OR=1.22，p=0.0086）、MA 和 MO 显着相关。未发现 c.28A>G KCNK18、c.328T>C KCNK18 和总体偏头痛的关联。