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

Abstract

In order to systematically test the hypothesis that genetic variation in the dopamine system contributes to the susceptibility to migraine with aura (MA), we performed a comprehensive genetic association study of altogether ten genes from the dopaminergic system in a large German migraine with aura case-control sample. Based on the genotyping results of 53 variants across the ten genes in 270 MA cases and 272 controls, three genes-DBH, DRD2 and SLC6A3-were chosen to proceed to additional genotyping of 380 MA cases and 378 controls. Four of the 26 genotyped polymorphisms in these three genes displayed nominally significant allelic P-values in the sample of 650 MA patients and 650 controls. Three of these SNPs [rs2097629 in DBH (uncorrected allelic P value = 0.0012, OR = 0.77), rs7131056 in DRD2 (uncorrected allelic P value = 0.0018, OR = 1.28) and rs40184 in SLC6A3 (uncorrected allelic P value = 0.0082, OR = 0.81)] remained significant after gene-wide correction for multiple testing by permutation analysis. Further consideration of imputed genotype data from 2,937 British control individuals did not affirm the association with DRD2, but supported the associations with DBH and SLC6A3. Our data provide new evidence for an involvement of components of the dopaminergic system-in particular the dopamine-beta hydroxylase and dopamine transporter genes-to the pathogenesis of migraine with aura.

Association of C/T polymorphism in intron 14 of the dopamine transporter gene (rs40184) with major depression in a northeastern Thai population

“…The impact of the rs40184 polymorphism on the susceptibility of MDD is of immense interest since it has been recently shown to be associated with specific neuropsychiatric and neurological disorders (Haeffel et al, 2008;Zhou et al, 2008;Mick et al, 2008;Todt et al, 2009). Although the molecular connection between this SNP and cellular DAT1 level has not been demonstrated, many reports in the literature link polymorphisms of unknown function to certain psychiatric diseases (Cook Jr. et al, 1995).…”

“…This particular SNP has also been found to play a genetic role in certain neuropsychiatric and neurological illnesses such as attention deficit hyperactivity disorder (Zhou et al, 2008), bipolar disorder (Mick et al, 2008) and migraine with aura (Todt et al, 2009). With regard to the genotyping technologies used in the research findings addressed above, the rs40184 polymorphism was genotyped on one of the high-throughput platforms, particularly Sequenom, Taqman and Illumina.…”

Dopaminergic symptoms in migraine

“…The migraine risk seems increased in ANKK1 DRD2 loci missense polymorphism or DBH rs7239728 polymorphism carriers and lowered in DRD2 rs6275 polymorphism carriers [16]. Migraine with aura is associated with polymorphisms in DBH (rs2097629), DRD2 (rs7131056) and the dopamine transporter gene SLC6A3 (rs40184) [17]. 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].…”

Hormonally modulated migraine is associated with single-nucleotide polymorphisms within genes involved in dopamine metabolism

“…Genetic polymorphisms in COMT (rs4680), TH (rs 6356 and rs2070762), solute carrier family 6 [28]) have been found to be associated with migraine [29][30][31][32][33][34][35][36][37][38]. However, the vast majority of SNP associations listed above have not been replicated [31].…”