Original Investigation

Human Genetics

, Volume 125, Issue 3, pp 265-279

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

  • Unda TodtAffiliated withInstitute of Human Genetics, University of CologneInstitute for Genetics, University of CologneCenter for Molecular Medicine, University of Cologne
  • , Christian NetzerAffiliated withInstitute of Human Genetics, University of CologneInstitute for Genetics, University of CologneCenter for Molecular Medicine, University of Cologne
  • , Mohammad ToliatAffiliated withInstitute for Genetics, University of CologneCologne Center for Genomics, University of Cologne
  • , Axel HeinzeAffiliated withKiel Pain and Headache Centre
  • , Ingrid GoebelAffiliated withInstitute of Human Genetics, University of CologneInstitute for Genetics, University of CologneCenter for Molecular Medicine, University of Cologne
  • , Peter NürnbergAffiliated withInstitute for Genetics, University of CologneCologne Center for Genomics, University of CologneCologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne
  • , Hartmut GöbelAffiliated withKiel Pain and Headache Centre
  • , Jan FreudenbergAffiliated withCenter for Genomics and Human Genetics, Feinstein Institute for Medical Research, Northshore-LIJ University Hospital
  • , Christian KubischAffiliated withInstitute of Human Genetics, University of CologneInstitute for Genetics, University of CologneCenter for Molecular Medicine, University of CologneCologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne Email author 

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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.