Journal of Neural Transmission

, Volume 115, Issue 1, pp 91–95

Family-based association analysis of functional VNTR polymorphisms in the dopamine transporter gene in migraine with and without aura

  • A. Karwautz
  • S. Campos de Sousa
  • A. Konrad
  • H.-E. Zesch
  • G. Wagner
  • A. Zormann
  • C. Wanner
  • G. Breen
  • M. Ray
  • C. Kienbacher
  • S. Natriashvili
  • D. A. Collier
  • C. Wöber
  • Ç. Wöber-Bingöl
Article

Summary.

Because of the role of dopamine in triggering migraine attacks, genes of the dopamine system are candidates for involvement in migraine. We examined three VNTR polymorphisms in the dopamine transporter, the 5′UTR VNTR, the intron 8 VNTR and the intron 14 VNTR, in a sample of 205 family trios. We used the transmission disequilibirium test (TDT) to examine the transmission of these three markers and their haplotypes to offspring affected by migraine. We found no significant transmission distortion of any marker. Likewise haplotypes of the three markers did not show significant overall or individual association with migraine. Finally we examined migraine with and without aura, and likewise found no association between dopamine transporter VNTRs or their haplotypes and either classification of the disease. We conclude that functional genetic variation in the dopamine transporter does not act as a significant risk factor for migraine.

Keywords: Migraine; DAT; gene 

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References

  1. Brookes, K, Xu, X, Chen, W,  et al. 2006The analysis of 51 genes in DSM-IV combined type attention deficit hyperactivity disorder: association signals in DRD4, DAT1 and 16 other genesMol Psychiatry111139CrossRefGoogle Scholar
  2. Campos de Sousa, S, Karwautz, A, Wöber, C, Wagner, G, Breen, G, Zesch, H-E, Konrad, A, Zormann, A, Wanner, C, Kienbacher, C, Collier, DA, Wöber-Bingöl, C 2007A DRD4 exon 3 VNTR allele protecting against migraine without auraAnn Neurol61574578CrossRefGoogle Scholar
  3. Cerbo, R, Barbanti, P, Buzzi, MG,  et al. 1997Dopamine hypersensitivity in migraine: role of the apomorphine testClin Neuropharmacol203641PubMedCrossRefGoogle Scholar
  4. Chen, SC 2006Epilepsy and migraine: the dopamine hypothesesMed Hypotheses66466472PubMedCrossRefGoogle Scholar
  5. Del Zompo, M, Cherchi, A, Palmas, MA, Ponti, M, Bocchetta, A, Gessa, GL, Piccardi, MP 1998Association between dopamine receptor genes and migraine without aura in a Sardinian sampleNeurology51781786PubMedGoogle Scholar
  6. Dichgans, M, Forderreuther, S, Deiterich, M, Pfaffenrath, V, Gasser, T 1998The D2 receptor NcoI allele: absence of allelic association with migraine with auraNeurology51928PubMedGoogle Scholar
  7. Dudbridge, F 2003Pedigree disequilibrium tests for multilocus haplotypesGenet Epidemiol25115121PubMedCrossRefGoogle Scholar
  8. Fanciullaci, M, Rosso, AD 2000Dopamine involvement in the migraine attackFunct Neurol15171181Google Scholar
  9. Fernandez, F, Lea, RA, Colson, NJ, Bellis, C, Quinlan, S, Griffiths, LR 2006Association between a 19 bp deletion polymorphism at the dopamine beta-hydroxylase (DBH) locus and migraine with auraJ Neurol Sci251118123PubMedCrossRefGoogle Scholar
  10. Freeman, B, Powell, J, Ball, D, Hill, L, Craig, I, Plomin, R 1997DNA by mail: an in expensive and noninvasive method for collecting DNA samples from widely dispersed populationsBehav Genet27251257PubMedCrossRefGoogle Scholar
  11. Gelfand, Y, Rodriguez, A, Benson, G 2007TRDB – the Tandem Repeats DatabaseNucleic Acids Res35D80D87PubMedCrossRefGoogle Scholar
  12. Gervil, M, Ulrich, V, Kyvik, KO, Olesen, J, Russell, MB 1999The relative role of genetic and environmental factors in migraine without auraNeurology53995999PubMedGoogle Scholar
  13. Greenwood, TA, Kelsoe, JR 2003Promoter and intronic variants affect the transcriptional regulation of the human dopamine transporter geneGenomics82511520PubMedCrossRefGoogle Scholar
  14. Greenwood, TA, Schork, NJ, Eskin, E, Kelsoe, JR 2006Identification of additional variants within the human dopamine transporter gene provides further evidence for an association with bipolar disorder in two independent samplesMol Psychiatry11125133PubMedCrossRefGoogle Scholar
  15. Grunhage, F, Schulze, TG, Muller, DJ,  et al. 2000Systematic screening for DNA sequence variation in the coding region of the human dopamine transporter gene (DAT1)Mol Psychiatry5275282PubMedCrossRefGoogle Scholar
  16. Guindalini, C, Howard, M, Haddley, K,  et al. 2006A dopamine transporter gene functional variant associated with cocaine abuse in a Brazilian sampleProc Natl Acad Sci USA10345524557PubMedCrossRefGoogle Scholar
  17. Headache Classification Subcommittee of the International Headache Society2004The International Classification of headache disorders, 2nd ednCephalalgia248160Google Scholar
  18. Hill, WG, Weir, BS 1994Maximum-likelihood estimation of gene location by linkage disequilibriumAm J Hum Genet54705714PubMedGoogle Scholar
  19. Karwautz, AFK, Campos de Sousa, S, Wöber, C,  et al. 2007Family-based analysis of serotonin transporter gene polymorphisms in migraine with and without auraCephalalgia27773780PubMedCrossRefGoogle Scholar
  20. Lea, RA, Dohy, A, Jordan, K, Quinlan, S, Brimage, PJ, Griffiths, LR 2000Evidence for allelic association of the dopamine beta-hydroxylase gene (DBH) with susceptibility to typical migraineNeurogenetics33540PubMedGoogle Scholar
  21. Maude, S, Curtin, J, Breen, G, Collier, D, Russell, G, Shaw, D, Clair, DS 2001The – 141C Ins/Del polymorphism of the dopamine D2 receptor gene is not associated with either migraine or Parkinson’s diseasePsychiatry Genet114952CrossRefGoogle Scholar
  22. Mochi, M, Cevoli, S, Cortelli, P, Pierangeli, G, Soriani, S, Scapoli, C, Montagna, P 2003A genetic association study of migraine with dopamine receptor 4, dopamine transporter and dopamine-beta-hydroxylase genesNeurol Sci23301305PubMedCrossRefGoogle Scholar
  23. Peroutka, SJ 1997Dopamine and migraineNeurology49650656PubMedGoogle Scholar
  24. Peroutka, SJ, Price, SC, Wilhoit, TL, Jones, KW 1998Comorbid migraine with aura, anxiety, and depression is associated with dopamine D2 receptor (DRD2) NcoI allelesMol Med41421PubMedGoogle Scholar
  25. Peroutka, SJ, Wilhoit, T, Jones, K 1997Clinical susceptibility to migraine with aura is modified by dopamine D2 receptor (DRD2) NcoI allelesNeurology49201206PubMedGoogle Scholar
  26. Plomin, R, Crabbe, J 2000DNAPsychol Bull126806828PubMedCrossRefGoogle Scholar
  27. Plomin, R, Rutter, M 1998Child development, molecular genetics, and what to do with genes once they are foundChild Dev6912231242PubMedCrossRefGoogle Scholar
  28. Rebaudengo, N, Rainero, I, Parziale, A, Rosina, F, Pavanelli, E, Rubino, E, Mazza, C, Ostacoli, L, Furlan, PM 2004Lack of interaction between a polymorphism in the dopamine D2 receptor gene and the clinical features of migraineCephalalgia24503507PubMedCrossRefGoogle Scholar
  29. Shepherd, AG, Lea, RA, Hutchins, C, Jordan, KL, Brimage, PJ, Griffiths, LR 2002Dopamine receptor genes and migraine with and without aura: an association studyHeadache42346351PubMedCrossRefGoogle Scholar
  30. Slatkin, M, Excoffier, L 1996Testing for linkage disequilibrium in genotypic data using the expectation-maximization algorithmHeredity76377383PubMedGoogle Scholar
  31. Stochino, ME, Asuni, C, Congiu, D, Del Zompo, M, Severino, G 2003Association study between the phenotype migraine without aura-panic disorder and dopaminergic receptor genesPharmacol Res48531534PubMedCrossRefGoogle Scholar
  32. Ulrich, V, Gervil, M, Kyvik, KO, Olesen, J, Russell, MB 1999Evidence of a genetic factor in migraine with aura: a population-based Danish twin studyAnn Neurol45242246PubMedCrossRefGoogle Scholar
  33. Vandenbergh, DJ, Persico, AM, Hawkins, AL, Griffin, CA, Li, X, Jabs, EW, Uhl, GR 1992Human dopamine transporter gene (DAT1) maps to chromosome 5p15.3 and displays a VNTRGenomics1411041106PubMedCrossRefGoogle Scholar
  34. VanNess, SH, Owens, MJ, Kilts, CD 2005The variable number of tandem repeats element in DAT1 regulates in vitro dopamine transporter densityBMC Genet655PubMedCrossRefGoogle Scholar
  35. Wöber-Bingöl, C, Wöber, C, Karwautz, A,  et al. 1995Diagnosis of headache in childhood and adolescence: a study in 437 patientsCephalalgia151321PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • A. Karwautz
    • 1
  • S. Campos de Sousa
    • 2
  • A. Konrad
    • 1
  • H.-E. Zesch
    • 1
  • G. Wagner
    • 1
  • A. Zormann
    • 1
  • C. Wanner
    • 1
  • G. Breen
    • 2
  • M. Ray
    • 1
  • C. Kienbacher
    • 1
  • S. Natriashvili
    • 1
  • D. A. Collier
    • 2
  • C. Wöber
    • 3
  • Ç. Wöber-Bingöl
    • 1
  1. 1.Headache Outpatient Centre, Department of Child and Adolescent PsychiatryMedical University of ViennaViennaAustria
  2. 2.Social, Genetic and Developmental Centre at the Institute of PsychiatryUniversity of LondonLondonUK
  3. 3.Headache Group, Department of NeurologyMedical University of ViennaViennaAustria

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