Association between migraine and endothelin type A receptor (ETA-231 A/G) gene polymorphism

Background: Previous studies have described an association between migraine and endothelin, a potent vasoconstrictor. Objective: To test the association between migraine and gene polymorphisms of the endothelin system. Methods: A population-based study of elderly individuals (n - 1,188) in Nantes (western France) was conducted. Lifetime migraine was defined according to the International Headache Society criteria, after an interview with a headache specialist. Five polymorphisms in genes encoding endothelin 1, endothelin type A (ET,), and type B receptors were determined in more than 90% of the sample. Results: Migraine was diagnosed in 140 participants (11.9%). The ETA (-231 A/G) polymorphism was the only polymorphism significantly associated with migraine. There was a trend of decreasing prevalence of migraine with number of copies of the G allele (AA genotype: 15.7% of participants with migraine, AG: 9.7%, GG: 2.9%; p < 0.001). Carrying the G allele was associated with a sex- and age-adjusted odds ratio of 0.50 (95% CI, 0.34 to 0.74). The association was observed in both sexes and was stronger in participants with a family history of severe headaches than in those without. Conclusions: A variant of the ET, receptor gene modulates the risk for migraine. These results offer new insights into the pathophysiology of the vascular component of migraine.