New genetic evidence for involvement of the dopamine system in migraine with aura.
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.
Todt
Unda
U
Institute of Human Genetics, University of Cologne, Germany.
Netzer
Christian
C
Toliat
Mohammad
M
Heinze
Axel
A
Goebel
Ingrid
I
Nürnberg
Peter
P
Göbel
Hartmut
H
Freudenberg
Jan
J
Kubisch
Christian
C
D000483:Alleles; D001483:Base Sequence; D016022:Case-Control Studies; D017931:DNA Primers / Q000235:genetics; D004298:Dopamine / Q000235:genetics*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics; D004299:Dopamine beta-Hydroxylase / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D005858:Germany; D006239:Haplotypes; D006801:Humans; D008297:Male; D020325:Migraine with Aura / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D017448:Receptors, Dopamine D2 / Q000235:genetics
D017931:DNA Primers; D050483:Dopamine Plasma Membrane Transport Proteins; D005819:Genetic Markers; D017448:Receptors, Dopamine D2; C493214:SLC6A3 protein, human; D004299:Dopamine beta-Hydroxylase; D004298:Dopamine