Clinical susceptibility to migraine with aura is modified by dopamine D2 receptor (DRD2) NcoI alleles.
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.
Peroutka
S J
SJ
Spectra Biomedical, Inc., Menlo Park, CA 94025, USA.
Wilhoit
T
T
Jones
K
K
D000328:Adult; D000483:Alleles; D005260:Female; D005838:Genotype; D006220:Haloperidol / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D008881:Migraine Disorders / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology*; D017448:Receptors, Dopamine D2 / Q000235:genetics*
D017448:Receptors, Dopamine D2; D006220:Haloperidol