The interplay of two single nucleotide polymorphisms in the CACNA1A gene may contribute to migraine susceptibility

Mara D'Onofrio, Anna Ambrosini, Alessandra Di Mambro, Ivan Arisi, Filippo M. Santorelli, Gaetano S. Grieco, Ferdinando Nicoletti, Giuseppe Nappi, Francesco Pierelli, Jean Schoenen, Maria Gabriella Buzzi

Research output: Contribution to journalArticlepeer-review


Migraine is a common disorder with a significant genetic component. Mutations in the CACNA1A gene are found in hemiplegic migraine (HM). Basilar-type (BM), another subtype of migraine with aura, differs from HM only by the absence of motor deficits. BM and HM may thus share common genetic features. In the present study, two single nucleotide polymorphisms (SNPs) of the CACNA1A gene were characterized in a population of migraine patients and healthy controls. The polymorphisms, E918D, predicting a glutamic acid-to-aspartic acid substitution at codon 918 and E993V, predicting a glutamic acid-to-valine substitution at codon 993, were frequently detected among patients and controls. Seven BM, 10 SHM, 5 FHM, 57 migraine with typical aura, 32 migraine without aura patients and 107 healthy controls were screened. The E918D and E993V SNPs were found in 30/117 (25.6%) and 32/117 (27.3%) migraine patients, respectively. The prevalence of these SNPs taken separately was not significantly different from that of control subjects (n = 28/107, 26.2% for E918D; n = 29/107 for E993V, 27.1%) neither for the total migraine population nor for the various migraine subtypes. By contrast, coexistence of both SNPs was more frequent in migraineurs (25/117, 21%) than in healthy controls (12/107, 11%; p = 0.048), a difference that was significant for every migraine subtype. This result suggests that the interplay of minor genetic variants such as single nucleotide polymorphisms may influence the P/Q-type calcium channel function in several subtypes of migraine.

Original languageEnglish
Pages (from-to)12-15
Number of pages4
JournalNeuroscience Letters
Issue number1
Publication statusPublished - Mar 27 2009


  • Basilar-type migraine
  • Hemiplegic migraine
  • Migraine
  • SNPs

ASJC Scopus subject areas

  • Neuroscience(all)


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