[Genetics of migraines: from ionic channels to single nucleotide polymorphisms?].
Our knowledge about migraine pathogenesis has increased exponentially over the last decade and this greatly due to the advances in genetics. In familial hemiplegic migraine (FHM), the findings of mutations in the CACNA1A gene (19p13), coding for the pore-forming subunit (alpha1A) of neuronal voltage-dependent P/Q-type calcium channels (FHM1), and in the ATP1A2 gene (1q21-23), encoding the alpha2-subunit of the Na+, K+ ATPase ionic pump (FHM2) have focused attention on central nervous system ionic channels and helped to better understand FHM pathophysiology. A dysfunction of these channels modifies neuronal excitability (favouring spreading depression), chemical neurotransmission and, indirectly, neuronal metabolism. These channels may represent targets for novel anti-migraine drugs, which underscores their importance for the frequent forms of migraine (without or with aura). Studies of gene associations, neuromuscular transmission, cerebellar functions, neuronal excitability and metabolism and certain drug effects suggest indeed that ionic channels play a pathogenic role in migraine with aura patients. However, in the majority of patients they are probably not the sole culprit, since most of the frequent forms of migraine seem to have a more complex genetic predisposition based on a number of single nucleotide polymorphisms. The challenge for the next decade is to establish correlations between the geno- and the phenotype of migraine patients which needs more frequent and focused genetic studies and a more precise phenotype, based on clinical as well as on neurophysiologic and metabolic data.
Fumal
A
A
Services de Neurologie et Neuroanatomie, Unité de Recherche sur les Céphalées, ULg.
Schoenen
J
J
D005838:Genotype; D006801:Humans; D007473:Ion Channels / Q000235:genetics* / Q000502:physiology; D008881:Migraine Disorders / Q000209:etiology / Q000235:genetics* / Q000503:physiopathology; D009154:Mutation; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide
D007473:Ion Channels