Evidence of syntaxin 1A involvement in migraine susceptibility: a Portuguese study.

OBJECTIVE To confirm syntaxin 1A as a risk factor for migraine, given that syntaxin 1A interacts with several factors in migraine pathophysiology. DESIGN Case-control approach. SETTING An outpatient clinic. PARTICIPANTS In a sample of 188 migraineurs (111 without aura and 77 with aura) and 287 migraine-free controls, 3 tagging SNPs of STX1A (rs3793243, rs941298, and rs6951030) were analyzed. A backward stepwise multiple logistic regression was performed. Allelic and haplotypic frequencies were compared between cases and controls. RESULTS We found that rs941298 and rs6951030 were risk factors for migraines. In particular, the TT genotype of rs941298 is associated with an increased risk of both migraine in general and migraine without aura; the GG and GT genotypes for rs6951030 are also associated with migraine, while the GT genotype of rs6951030 was found to be significant in the migraine without aura group. The single-nucleotide polymorphism rs3793243 did not show any significant association. In the haplotype-based analysis, we found an underrepresentation of the T-C-T haplotype (rs3793243-rs941298-rs6951030) in the global sample and in migraine without aura group. We found an enrichment of the G allele of rs6951030 for female migraineurs only. CONCLUSIONS We confirmed the involvement of syntaxin 1A in migraine susceptibility regarding rs941298. In addition, we found rs6951030 to also be associated in Portuguese migraine patients. Sex differences should be further explored to disentangle a possible sex susceptibility in syntaxin 1A.