The Pathophysiological and Pharmacological Basis of Current Drug Treatment of Migraine Headache

Doodipala Samba Reddy

Disclosures

Expert Rev Clin Pharmacol. 2013;6(3):271-288. 

In This Article

Migraine Genetics

Migraine is a complex genetic disorder with polygenic multifactorial inheritance.[10–12,39–44] There is a genetic component in migraine with defects in ion channels, known as 'channelopathies'. Since ion channels are the principal mediators of cellular excitability, distinct channelopathies may underlie the CSD[24] or other related excitatory–inhibitory balances in the brain.[10] However, such channelopathies are very rare, and have been found in a few families with hemiplegic migraine. Familial hemiplegic migraine (FHM), a rare monogenic autosomal dominant form of MA, is widely studied and has contributed to the current understanding of the genetics of migraine.[11,12] A typical FHM attack resembles episodic MA, suggesting that FHM and MA share similar pathogenetic mechanisms. Three causative genes have been identified for FHM.[40–44] FHM1 is caused by missense mutations in CACNA1A, the gene encoding the pore-forming subunit of neuronal Cav2.1 (P/Q-type) voltage-gated calcium channels.[40,44] FHM2 is caused by mutations in ATP1A2, the gene encoding the α2-subunit of the Na+/K+ ATPase.[16,19] FHM3 is caused by missense mutations in SCNA1A, the gene encoding the pore-forming subunit of the neural NaV1.1 voltage-gated sodium channels.[11,42] However, further genetic studies are needed to characterize FHM genes in MA or MO, depending on the mutation.

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