Analysis of Genetic Variants in SCN1A, SCN2A, KCNK18, TRPA1 and STX1A as a Possible Marker of Migraine

Marta Kowalska; Michał Prendecki; Magdalena Kapelusiak-Pielok; Teresa Grzelak; Urszula Łagan-Jędrzejczyk; Małgorzata Wiszniewska; Wojciech Kozubski; Jolanta Dorszewska

doi:10.2174/1389202921666200415181222

Analysis of Genetic Variants in SCN1A, SCN2A, KCNK18, TRPA1 and STX1A as a Possible Marker of Migraine

Curr Genomics. 2020 Apr;21(3):224-236. doi: 10.2174/1389202921666200415181222.

Authors

Marta Kowalska¹, Michał Prendecki¹, Magdalena Kapelusiak-Pielok¹, Teresa Grzelak¹, Urszula Łagan-Jędrzejczyk¹, Małgorzata Wiszniewska¹, Wojciech Kozubski¹, Jolanta Dorszewska¹

Affiliation

¹ 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.

Abstract

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.

Keywords: Ion channels; genetic biomarker; genotyping; migraine; polygenetic disease; polymorphisms.