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 associati on between migraine and gene polymorphisms of the endothelin system. Method s: A population-based study of elderly individuals (n - 1,188) in Nantes (w estern France) was conducted. Lifetime migraine was defined according to th e International Headache Society criteria, after an interview with a headac he specialist. Five polymorphisms in genes encoding endothelin 1, endotheli n type A (ET,), and type B receptors were determined in more than 90% of th e sample. Results: Migraine was diagnosed in 140 participants (11.9%). The ETA (-231 A/G) polymorphism was the only polymorphism significantly associa ted with migraine. There was a trend of decreasing prevalence of migraine w ith number of copies of the G allele (AA genotype: 15.7% of participants wi th migraine, AG: 9.7%, GG: 2.9%; p < 0.001). Carrying the G allele was asso ciated with a sex- and age-adjusted odds ratio of 0.50 (95% CI, 0.34 to 0.7 4). The association was observed in both sexes and was stronger in particip ants with a family history of severe headaches than in those without. Concl usions: 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.