Kowalska Marta, Prendecki Michał, Kapelusiak-Pielok Magdalena, Grzelak Teresa, Łagan-Jędrzejczyk Urszula, Wiszniewska Małgorzata, Kozubski Wojciech, Dorszewska Jolanta
1Laboratory of Neurobiology, Department of Neurology, Poznan University of Medical Sciences, Poznan, Poland; 2Department of Neurology, Poznan University of Medical Sciences, Poznan, Poland; 3Department of Physiology, Poznan University of Medical Sciences, Poznan, Poland; 4Faculty of Health Care, Stanislaw Staszic University of Applied Sciences in Pila, Pila, Poland; 5Department of Neurology, Specialistic Hospital in Pila, Pila, Poland.
Curr Genomics. 2020 Apr;21(3):224-236. doi: 10.2174/1389202921666200415181222.
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).
The aim of the study was to analyze the following variants of genes encoding ion channels and associated protein: c.3199G>A , c.56G>A , c.28A>G and c.328T>C , c.3053A>G , c.31-1811C>T in migraine patients.
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 and c.31-1811C>T .
AA genotype of c.56G>A was found only in migraine patients. Patients with c.328T>C mutation had an increased risk of developing migraine before the age of 18. Moreover, individuals with AA/TC haplotype of had higher attack frequency than those with AA/TT (p<0.05). T allele of c.31-1811C>T was more frequent in MA patients than MO (p<0.05). The c.3053A>G polymorphism was more common in patients with migraine onset before the age of 15 (p<0.05), while c.31-1811C>T and c.3199G>A before the age of 10 (p<0.01). Meta-analysis showed a significant association of c.31-1811C>T polymorphism with migraine overall (OR=1.22, p=0.0086), MA, and MO. No association was found for c.28A>G , c.328T>C and migraine overall.
Changes in genes encoding ion channels or proteins regulating their functioning may increase the risk of migraines and correlate with clinical features of disease, . age of onset and attack frequency.
偏头痛是一种多基因疾病，被认为是一种通道病。基因变化导致的离子功能失调可能会激活三叉神经血管系统，并诱发偏头痛发作，包括有先兆偏头痛（MA）和无先兆偏头痛（MO）。
本研究旨在分析偏头痛患者中编码离子通道及相关蛋白的基因的以下变异：c.3199G>A、c.56G>A、c.28A>G、c.328T>C、c.3053A>G、c.31-1811C>T。
本研究纳入了170例偏头痛患者和173例对照。采用高分辨率熔解曲线分析（HRMA）和桑格测序进行基因分型。对c.28A>G、c.328T>C和c.31-1811C>T进行荟萃分析。
仅在偏头痛患者中发现了c.56G>A的AA基因型。携带c.328T>C突变的患者在18岁之前患偏头痛的风险增加。此外，具有AA/TC单倍型的个体比具有AA/TT单倍型的个体发作频率更高（p<0.05）。c.31-1811C>T的T等位基因在MA患者中比MO患者中更常见（p<0.05）。c.3053A>G多态性在15岁之前发病的偏头痛患者中更常见（p<0.05），而c.31-1811C>T和c.3199G>A在10岁之前更常见（p<0.01）。荟萃分析显示c.31-1811C>T多态性与总体偏头痛（OR=1.22，p=0.0086）、MA和MO显著相关。未发现c.28A>G、c.328T>C与总体偏头痛之间存在关联。
编码离子通道或调节其功能的蛋白质基因的变化可能会增加患偏头痛的风险，并与疾病的临床特征，如发病年龄和发作频率相关。
