Calcium Signaling Related Genes in Migraine

Abstract

Calcium is essential for the growth of neurons during infancy as well as transmission of signals between neurons; thus, the related signaling pathways might contribute to the pathogenesis of brain disorders. Voltage-gated calcium channels are widely expressed in the trigeminovascular system and are regarded as important contributors to some forms of familial migraines. In fact, these channels participate in the migraine initiation events. We compared the expression of genes coding for ion channels, including SLC1A1, SLC25A12, ATP2B2, and their associated lncRNAs, namely LINC01231, lnc-SLC25A12, and lnc-MTR-1, between migraineurs and healthy controls. All mentioned genes and lncRNAs, except for ATP2B2 and LINC01231, were shown to be up-regulated in total migraineurs compared with controls. Moreover, the expression levels of ATP2B2 were higher in patients with aura compared with those without aura (Expression ratio (95% CI) = 5.83 (2.93–11.59), p < 0.0001). Yet, SLC25A12 was down-regulated in patients with aura as compared with those without aura (Expression ratio (95% CI) = 0.21 (0.11–0.42), p = 0.004). Notably, we demonstrated high specificity and sensitivity values for some genes in the differentiation of migraineurs from healthy controls. Taken together, we demonstrated significant over-expression of a number of ion channel and transporter genes and their related lncRNAs in migraineurs and suggested these genes as potential markers for this neurological condition.