Migraine is a common
neurological disorder with a complex inheritance pattern. Mutations in genes encoding
proteins that are involved in ion transport across the neuronal membrane have been linked to rare monogenic variants of
migraine. These or other related genes and
proteins are also candidates to be involved in the inherited predisposition to the more common forms of
migraine without aura (MO) or
migraine with aura (MA). One of these
proteins, syntaxin 1A, encoded by the STX1A gene, is a key molecule in
ion channel regulation and synaptic exocytosis. We assessed the contribution of STX1A to
migraine by analyzing three SNPs that cover the entire gene (rs6951030-rs941298-rs4363087), in a case-control association study in 210
migraine patients (102 MO, 86 MA, 22 hemiplegic
migraine) and 210 sex-matched unrelated controls. The single-marker analysis revealed significant differences in both allele frequencies (P=0.0087, OR=1.48) and genotype distributions (P=0.0133) of the rs941298 SNP between migraineurs and controls, with an overrepresentation of T-allele carriers in the
migraine sample (OR=1.78). We subsequently performed a haplotype-based analysis and observed evidence of an overrepresentation of the A-T-G (rs6951030-rs941298-rs4363087) allelic combination in
migraine patients and an increased frequency of carriers of this risk haplotype (P=0.008, OR=1.71). These differences remained significant when patients were subdivided into MO and MA. When the control series was enlarged for rs941298, we confirmed the association only with the whole
migraine group.