Functional polymorphisms of the 5-HT1A and 5-HT1B receptor are associated with clinical symptoms in migraineurs

Migraine is regarded as a polygenic disease and serotonergic pathways appear to play a major role in its pathogenesis. In the present study, the role of the 5-HT1A and 5-HT1B receptors in migraine was evaluated. The human 5-HT1A receptor gene transcription is modulated by a functional C-1019G promoter polymorphism. The 5-HT1B receptor is the main effector of vasoconstriction in meningeal and cerebral arteries and its functional G861C promoter polymorphism was investigated. We report a positive association of the GG genotype of the 5-HT1A promoter polymorphism with avoidance of physical activity during a migraine attack in comparison to the CC genotype (p = 0.008). Moreover, a positive association of the CC genotype of the G861C polymorphism of the 5-HT1B receptor with the reported intensity of the headache attack on the visual analogue scale was observed (CC 8.3 +/- 1.5 vs. GG 6.9 +/- 1.8; p < 0.05). An association of either polymorphism with migraine with or without aura could not be found. For the first time, our results indicate a role of allelic variation of the 5-HT1A receptor in motion related discomfort in migraineurs and a role of the 5-HT1B receptor polymorphism in headache intensity.