A280V polymorphism in the histamine H3 receptor as a risk factor for migraine.

ABSTRACT

BACKGROUND AND AIMS: Activation of histamine H3 receptors blocks the release of peptides responsible for headache. Our objective was to investigate the association between the genotypes of A280V polymorphism in the H3 receptor and migraine risk. METHODS: We evaluated the frequency of the genotypes of A280V, polymorphism A280V and allelic variants of H3 receptor in 147 migraine patients and 186 healthy controls using a PCR-RLFP method. RESULTS: V allele frequency was 6.46% and 2.68% for the cases and controls, respectively (p = 0.02) (OR 2.67; 95% CI 1.20-5.93). The frequency of V/V + V/A genotypes was 12.92% in migraine patients, significantly higher when compared to the 3.22% frequency in the control group (p = 0.001) (OR 4.45; 95% CI 1.7-11.46). CONCLUSIONS: The results of this study suggest that V-allele genotypes in the H3 receptor gene are related to migraine risk in the Mexican population. We propose the hypothesis that the V-allele genotypes in the H3 receptor gene increase the population of inactive receptors, enhancing the inhibition of the negative feedback mechanism on the H3 receptor and increasing histamine release, which correlates with migraine attacks in susceptible patients. The case-control study reinforces the role of histamine in migraine pathogenesis.