Association study between the phenotype migraine without aura—panic disorder and dopaminergic receptor genes

New genetic evidence for involvement of the dopamine system in migraine with aura

“…On the contrary, the possible association between MA and the D2 dopamine receptor gene (DRD2) SNP rs7131056 was not aYrmed by the enlargement of the control sample. Previous genetic studies had reported inconsistent results for several variants at the DRD2 locus (a silent change at amino acid position His313 of DRD2 named "NcoI polymorphism" (Dichgans et al 1998;Peroutka et al 1997Peroutka et al , 1998Rebaudengo et al 2004;Stochino et al 2003), with the underlying SNP meanwhile termed rs61689984; a (possibly functional) insertion/deletion polymorphism in the promotor region designated "-141C Ins/ Del" (Maude et al 2001); and an intronic dinucleotide repeat (Del Zompo et al 1998;Stochino et al 2003). None of these markers was included in the HapMap project and information on possible linkage disequilibrium (LD) between these previously genotyped polymorphisms and the haplotype-tagging SNPs tested in our study are not available.…”

“…Many migraine candidate genes have been analyzed in case-control or family based association studies during the past 10 years, among these several genes from the dopamine pathway (Asuni et al 2007;Cevoli et al 2006;de Sousa et al 2007;Del Zompo et al 1998;Dichgans et al 1998;Lea et al 2000;Maude et al 2001;Mochi et al 2003;Noble 2003;Peroutka et al 1997Peroutka et al , 1998Rebaudengo et al 2004;Shepherd et al 2002;Stochino et al 2003). However, most of the results of these association studies were negative, and positive Wndings could very often not be replicated.…”

“…However, most of the results of these association studies were negative, and positive Wndings could very often not be replicated. The dopamine D2 receptor gene is an illustrative case: several groups analyzed diVerent polymorphisms in this gene in patients with MA and/or MO, and signiWcant Wndings were reported in some of these studies for some of the genotyped polymorphisms (Del Zompo et al 1998;Peroutka et al 1997Peroutka et al , 1998), but could not be conWrmed by other groups (Dichgans et al 1998;Rebaudengo et al 2004;Stochino et al 2003). Diverse reasons may contribute to these inconsistencies: inadequate sample sizes, arbitrarily chosen polymorphisms, existence of diVerent risk alleles in diVerent populations, inadequate corrections for multiple testing, phenotypic diVerences between study populations (in which e.g., patients with MA, MO, childhood migraine, or any common type of migraine were included), and/or publication bias towards studies with positive results.…”

Dopaminergic symptoms in migraine

“…The incidence of migraine with aura, major depression, generalized anxiety disorder, panic attacks and phobia is higher in individuals with the DRD2 NcoI C/C genotype than in those with a DRD2 NcoI T allele [18]. In their genetic studies, Stochino et al [19,20] reported that the DRD2/NcoI C allele could be a susceptibility factor for good rizatriptan responsiveness, but did not confirm an association between dopaminergic genes and the migraine-panic phenotype. Using a family-based association method, others have reported that the allelic distribution at the DRD2 locus differs significantly in the dopaminergic migraineurs subgroup [21], although a more recent study argued against a role for the DRD2 gene in the migraine clinical phenotype [22].…”

Increased Dopamine Is Associated With the cGMP and Homocysteine Pathway in Female Migraineurs

“…However, data are conflicting as some studies suggest that dopamine itself, or dopamine receptor agonists cause migraine pain, whereas others do not 2,3,11,12 . Investigations of genetic polymorphisms in dopamine genes especially in dopamine receptor genes, dopamine‐beta hydroxylase, and dopamine transporters have revealed very controversial results 13‐22 . There are as many, if not more, studies showing no relationship between dopamine genetics and migraine than there are those that do, so that no definitive conclusion can be drawn 1 .…”