Clinical susceptibility to migraine with aura is modified by dopamine D2 receptor (DRD2) NcoI alleles

• Published in: Neurology Vol. 49; no. 1; p. 201
• Main Authors: Peroutka, S J, Wilhoit, T, Jones, K
• Format: Journal Article
• Language: English
• Published: United States 01.07.1997
• Subjects: Adult; Alleles; Female; Genotype; Haloperidol - therapeutic use; Humans; Male; Middle Aged; Migraine Disorders - drug therapy; Migraine Disorders - genetics; Migraine Disorders - physiopathology; Receptors, Dopamine D2 - genetics
• ISSN: 0028-3878
• DOI: 10.1212/WNL.49.1.201

Migraine has a major genetic component. Although most recent scientific studies have focused on the role of 5-hydroxytryptamine and neuropeptides in migraine, dopaminergic systems are also implicated in the pathogenesis. Therefore, the dopamine D2 receptor (DRD2) was analyzed as a candidate gene since antagonists of this receptor have been reported to be effective in the acute treatment of migraine. Individuals with migraine with aura (n = 52) have an increased frequency (0.84) of the DRD2 NcoI C allele (chi-square = 6.47; p < 0.005) compared with control individuals (n = 121; C allele frequency = 0.71). Individuals with migraine without aura (n = 77) showed the same DRD2 T allele frequency (0.70) as the control group. Migraine with aura was present in 27% of the C/C individuals, 16% of the C/T individuals, and 5.2% of the T/T individuals. These data suggest that activation of the DRD2 receptor plays a modifying role in the pathophysiology of migraine with aura. As a result, these data provide a molecular rationale for the documented efficacy of DRD2 antagonists in the treatment of migraine with aura.