neurogenetics

, Volume 10, Issue 3, pp 199–208 | Cite as

Association between migraine and a functional polymorphism at the dopamine β-hydroxylase locus

  • F. Fernandez
  • N. Colson
  • S. Quinlan
  • J. MacMillan
  • R. A. Lea
  • L. R. Griffiths
Original Article

Abstract

Migraine is a common neurological disorder with a significant genetic component. Although a number of linkage and association studies have been undertaken, the number and identity of all migraine susceptibility genes has yet to be defined. The existence of dopaminergic hypersensitivity in migraine has been recognised on a pharmacological basis and some studies have reported genetic association between migraine and dopamine-related gene variants. Our laboratory has previously reported association of migraine with a promoter STR marker in the dopamine beta hydroxylase (DBH) gene. In the present study, we analysed two additional DBH markers in two independent migraine case–control cohorts. These two markers are putative functional SNPs, one within the promoter (−1021C→T) and another SNP (+1603C→T) in exon 11 of the DBH gene. The results showed a significant association for allelic and genotypic frequency distribution between the DBH marker in the promoter and migraine in the first (P = 0.004 and P = 0.012, respectively) and the second (P = 0.013 and P = 0.031, respectively) tested cohorts. There was no association observed between either genotype and/or allelic frequencies for the DBH marker located in exon 11 and migraine (P ≥ 0.05). The promoter DBH marker, reported associated with migraine in this study, has been shown to affect up to 52% of plasma DBH activity. Varying DBH activity levels have been postulated to be involved in migraine process with an increase of dopamine, resulting from a lower DBH activity shown positively correlated with migraine severity. It is plausible that the functional promoter variant of DBH may play a role in the migraine disorder.

Keywords

Migraine Genetic association DBH gene Functional polymorphism 

References

  1. 1.
    Abecasis GR, Cookson WO (2000) GOLD–graphical overview of linkage disequilibrium. Bioinformatics 16:182–183. doi:10.1093/bioinformatics/16.2.182 PubMedCrossRefGoogle Scholar
  2. 2.
    Anthony M (1981) Biochemical indices of sympathetic activity in migraine. Cephalalgia 1:83–89. doi:10.1111/j.1468-2982.1981.tb00014.x PubMedCrossRefGoogle Scholar
  3. 3.
    Barbanti P, Fabbrini G, Ricci A, Bruno G, Cerbo R, Bronzetti E, Amenta F, Luigi Lenzi G (2000) Reduced density of dopamine D2-like receptors on peripheral blood lymphocytes in Alzheimer’s disease. Mech Ageing Dev 120:65–75. doi:10.1016/S0047-6374(00)00183-4 PubMedCrossRefGoogle Scholar
  4. 4.
    Castillo J, Martinez F, Suarez C, Naveiro J, Lema M, Noya M (1996) Cerebrospinal fluid tyrosine and 3,4-dihydroxyphenylacetic acid levels in migraine patients. Cephalalgia 16:56–61. doi:10.1046/j.1468-2982.1996.1601056.x PubMedCrossRefGoogle Scholar
  5. 5.
    Cerbo R, Barbanti P, Buzzi MG, Fabbrini G, Brusa L, Roberti C, Zanette E, Lenzi GL (1997) Dopamine hypersensitivity in migraine: role of the apomorphine test. Clin Neuropharmacol 20:36–41. doi:10.1097/00002826-199702000-00004 PubMedCrossRefGoogle Scholar
  6. 6.
    Cubells JF, Kranzler HR, McCance-Katz E, Anderson GM, Malison RT, Price LH, Gelernter J (2000) A haplotype at the DBH locus, associated with low plasma dopamine beta-hydroxylase activity, also associates with cocaine-induced paranoia. Mol Psychiatry 5:56–63. doi:10.1038/sj.mp.4000657 PubMedCrossRefGoogle Scholar
  7. 7.
    Cubells JF, Price LH, Meyers BS, Anderson GM, Zabetian CP, Alexopoulos GS, Nelson JC, Sanacora G, Kirwin P, Carpenter L, Malison RT, Gelernter J (2002) Genotype-controlled analysis of plasma dopamine beta-hydroxylase activity in psychotic unipolar major depression. Biol Psychiatry 51:358–364. doi:10.1016/S0006-3223(01)01349-X PubMedCrossRefGoogle Scholar
  8. 8.
    Cubells JF, van Kammen DP, Kelley ME, Anderson GM, O’Connor DT, Price LH, Malison R, Rao PA, Kobayashi K, Nagatsu T, Gelernter J (1998) Dopamine beta-hydroxylase: two polymorphisms in linkage disequilibrium at the structural gene DBH associate with biochemical phenotypic variation. Hum Genet 102:533–540. doi:10.1007/s004390050736 PubMedCrossRefGoogle Scholar
  9. 9.
    Cubells JF, Zabetian CP (2004) Human genetics of plasma dopamine beta-hydroxylase activity: applications to research in psychiatry and neurology. Psychopharmacology (Berl) 174:463–476. doi:10.1007/s00213-004-1840-8 CrossRefGoogle Scholar
  10. 10.
    D’Andrea G, Granella F, Perini F, Farruggio A, Leone M, Bussone G (2006) Platelet levels of dopamine are increased in migraine and cluster headache. Headache 46:585–591. doi:10.1111/j.1526-4610.2006.00407.x PubMedCrossRefGoogle Scholar
  11. 11.
    Del Zompo M, Cherchi A, Palmas MA, Ponti M, Bocchetta A, Gessa GL, Piccardi MP (1998) Association between dopamine receptor genes and migraine without aura in a Sardinian sample. Neurology 51:781–786PubMedGoogle Scholar
  12. 12.
    Depondt C, Cock HR, Healy DG, Burley MW, Weinshenker D, Wood NW, Goldstein DB, Sisodiya SM (2004) The -1021C->T DBH gene variant is not associated with epilepsy or antiepileptic drug response. Neurology 63:1497–1499PubMedGoogle Scholar
  13. 13.
    Dobrowolski SF, Ellingson C, Coyne T, Grey J, Martin R, Naylor EW, Koch R, Levy HL (2007) Mutations in the phenylalanine hydroxylase gene identified in 95 patients with phenylketonuria using novel systems of mutation scanning and specific genotyping based upon thermal melt profiles. Mol Genet Metab 91:218–227. doi:10.1016/j.ymgme.2007.03.010 PubMedCrossRefGoogle Scholar
  14. 14.
    Fanciullacci M, Alessandri M, Del Rosso A (2000) Dopamine involvement in the migraine attack. Funct Neurol 15(Suppl 3):171–181PubMedGoogle Scholar
  15. 15.
    Fernandez F, Lea RA, Colson NJ, Bellis C, Quinlan S, Griffiths LR (2006) Association between a 19 bp deletion polymorphism at the dopamine beta-hydroxylase (DBH) locus and migraine with aura. J Neurol Sci 251:118–123. doi:10.1016/j.jns.2006.09.013 PubMedCrossRefGoogle Scholar
  16. 16.
    Fisher H (1997) Migraine research methods. CMAJ 157:1015–1016, 1018PubMedGoogle Scholar
  17. 17.
    Friberg L, Olesen J, Iversen HK, Sperling B (1991) Migraine pain associated with middle cerebral artery dilatation: reversal by sumatriptan. Lancet 338:13–17. doi:10.1016/0140-6736(91)90005-A PubMedCrossRefGoogle Scholar
  18. 18.
    Gallai V, Gaiti A, Sarchielli P, Coata G, Trequattrini A, Paciaroni M (1992) Evidence for an altered dopamine beta-hydroxylase activity in migraine and tension-type headache. Acta Neurol Scand 86:403–406PubMedCrossRefGoogle Scholar
  19. 19.
    Gervil M, Ulrich V, Olesen J, Russell MB (1998) Screening for migraine in the general population: validation of a simple questionnaire. Cephalalgia 18:342–348. doi:10.1046/j.1468-2982.1998.1806342.x PubMedCrossRefGoogle Scholar
  20. 20.
    Gotoh F, Kanda T, Sakai F, Yamamoto M, Takeoka T (1976) Serum dopamine-beta-hydroxylase activity in migraine. Arch Neurol 33:656–657PubMedGoogle Scholar
  21. 21.
    HCCIHS (2004) Headache Classification Committee for the International Headache Society. Classification and diagnostic criteria for headache disorders, cranial neuralgias and facial pain. 2nd edn. Cephalgia 24(Suppl 1):1–60Google Scholar
  22. 22.
    Healy DG, Abou-Sleiman PM, Ozawa T, Lees AJ, Bhatia K, Ahmadi KR, Wullner U, Berciano J, Moller JC, Kamm C, Burk K, Barone P, Tolosa E, Quinn N, Goldstein DB, Wood NW (2004) A functional polymorphism regulating dopamine beta-hydroxylase influences against Parkinson’s disease. Ann Neurol 55:443–446. doi:10.1002/ana.20063 PubMedCrossRefGoogle Scholar
  23. 23.
    Honkaniemi J, Liimatainen S, Rainesalo S, Sulavuori S (2006) Haloperidol in the acute treatment of migraine: a randomized, double-blind, placebo-controlled study. Headache 46:781–787. doi:10.1111/j.1526-4610.2006.00438.x PubMedCrossRefGoogle Scholar
  24. 24.
    Kirchmann M, Seven E, Bjornsson A, Bjornssdottir G, Gulcher JR, Stefansson K, Olesen J (2006) Validation of the deCODE Migraine Questionnaire (DMQ3) for use in genetic studies. Eur J Neurol 13:1239–1244. doi:10.1111/j.1468-1331.2006.01491.x PubMedCrossRefGoogle Scholar
  25. 25.
    Krypuy M, Ahmed AA, Etemadmoghadam D, Hyland SJ, DeFazio A, Fox SB, Brenton JD, Bowtell DD, Dobrovic A (2007) High resolution melting for mutation scanning of TP53 exons 5-8. BMC Cancer 7:168. doi:10.1186/1471-2407-7-168 PubMedCrossRefGoogle Scholar
  26. 26.
    Launer LJ, Terwindt GM, Ferrari MD (1999) The prevalence and characteristics of migraine in a population-based cohort: the GEM study. Neurology 53:537–542PubMedGoogle Scholar
  27. 27.
    Lea RA, Dohy A, Jordan K, Quinlan S, Brimage PJ, Griffiths LR (2000) Evidence for allelic association of the dopamine beta-hydroxylase gene (DBH) with susceptibility to typical migraine. Neurogenetics 3:35–40PubMedGoogle Scholar
  28. 28.
    Lipton RB, Bigal ME, Diamond M, Freitag F, Reed ML, Stewart WF (2007) Migraine prevalence, disease burden, and the need for preventive therapy. Neurology 68:343–349. doi:doi:10.1212/01.wnl.0000252808.97649.21 PubMedCrossRefGoogle Scholar
  29. 29.
    Lipton RB, Dodick D, Sadovsky R, Kolodner K, Endicott J, Hettiarachchi J, Harrison W (2003) A self-administered screener for migraine in primary care: the ID migraine validation study. Neurology 61:375–382PubMedGoogle Scholar
  30. 30.
    Lipton RB, Stewart WF (1993) Migraine in the United States: a review of epidemiology and health care use. Neurology 43:S6–S10PubMedGoogle Scholar
  31. 31.
    Martinez F, Castillo J, Rodriguez JR, Leira R, Noya M (1993) Neuroexcitatory amino acid levels in plasma and cerebrospinal fluid during migraine attacks. Cephalalgia 13:89–93. doi:10.1046/j.1468-2982.1993.1302089.x PubMedCrossRefGoogle Scholar
  32. 32.
    Mikamo K, Takeshima T, Takahashi K (1989) Cardiovascular sympathetic hypofunction in muscle contraction headache and migraine. Headache 29:86–89. doi:10.1111/j.1526-4610.1989.hed2902086.x PubMedCrossRefGoogle Scholar
  33. 33.
    Mochi M, Cevoli S, Cortelli P, Pierangeli G, Soriani S, Scapoli C, Montagna P (2003) A genetic association study of migraine with dopamine receptor 4, dopamine transporter and dopamine-beta-hydroxylase genes. Neurol Sci 23:301–305. doi:10.1007/s100720300005 PubMedCrossRefGoogle Scholar
  34. 34.
    Nahmias J, Burley MW, Povey S, Porter C, Craig I, Wolfe J (1992) A 19 bp deletion polymorphism adjacent to a dinucleotide repeat polymorphism at the human dopamine beta-hydroxylase locus. Hum Mol Genet 1:286. doi:10.1093/hmg/1.4.286 PubMedCrossRefGoogle Scholar
  35. 35.
    O’Connor DT, Cervenka JH, Stone RA, Levine GL, Parmer RJ, Franco-Bourland RE, Madrazo I, Langlais PJ, Robertson D, Biaggioni I (1994) Dopamine beta-hydroxylase immunoreactivity in human cerebrospinal fluid: properties, relationship to central noradrenergic neuronal activity and variation in Parkinson’s disease and congenital dopamine beta-hydroxylase deficiency. Clin Sci (Lond) 86:149–158Google Scholar
  36. 36.
    O’Connor TP, van der Kooy D (1988) Enrichment of a vasoactive neuropeptide (calcitonin gene related peptide) in the trigeminal sensory projection to the intracranial arteries. J Neurosci 8:2468–2476PubMedGoogle Scholar
  37. 37.
    Pasay C, Arlian L, Morgan M, Vyszenski-Moher D, Rose A, Holt D, Walton S, McCarthy J (2008) High-resolution melt analysis for the detection of a mutation associated with permethrin resistance in a population of scabies mites. Med Vet Entomol 22:82–88. doi:10.1111/j.1365-2915.2008.00716.x PubMedCrossRefGoogle Scholar
  38. 38.
    Peroutka SJ (1997) Dopamine and migraine. Neurology 49:650–656PubMedGoogle Scholar
  39. 39.
    Peroutka SJ (2004) Migraine: a chronic sympathetic nervous system disorder. Headache 44:53–64. doi:10.1111/j.1526-4610.2004.04011.x PubMedCrossRefGoogle Scholar
  40. 40.
    Peroutka SJ, Wilhoit T, Jones K (1997) Clinical susceptibility to migraine with aura is modified by dopamine D2 receptor (DRD2) NcoI alleles. Neurology 49:201–206PubMedGoogle Scholar
  41. 41.
    Pradalier A, Launay JM, Soliman M, Dreux C, Guittard M, Hanna KM, Dry J (1987) Platelet release of dopamine in the common migraine attack. Presse Med 16:1321–1323PubMedGoogle Scholar
  42. 42.
    Rasmussen BK, Jensen R, Olesen J (1991) Questionnaire versus clinical interview in the diagnosis of headache. Headache 31:290–295. doi:10.1111/j.1526-4610.1991.hed3105290.x PubMedCrossRefGoogle Scholar
  43. 43.
    Russell MB, Ulrich V, Gervil M, Olesen J (2002) Migraine without aura and migraine with aura are distinct disorders. A population-based twin survey. Headache 42:332–336. doi:10.1046/j.1526-4610.2002.02102.x PubMedCrossRefGoogle Scholar
  44. 44.
    Sanger GJ, Andrews PL (2006) Treatment of nausea and vomiting: gaps in our knowledge. Auton Neurosci 129:3–16. doi:10.1016/j.autneu.2006.07.009 PubMedCrossRefGoogle Scholar
  45. 45.
    Singaram C, Ashraf W, Gaumnitz EA, Torbey C, Sengupta A, Pfeiffer R, Quigley EM (1995) Dopaminergic defect of enteric nervous system in Parkinson’s disease patients with chronic constipation. Lancet 346:861–864. doi:10.1016/S0140-6736(95)92707-7 PubMedCrossRefGoogle Scholar
  46. 46.
    Siva A, Zarifoglu M, Ertas M, Saip S, Karli HN, Baykan B, Keskinaslan A, Senocak M (2008) Validity of the ID-migraine screener in the workplace. Neurology 70:1337–1345. doi:10.1212/01.wnl.0000309221.85545.0d PubMedCrossRefGoogle Scholar
  47. 47.
    Suzuki N, Hardebo JE (1993) The cerebrovascular parasympathetic innervation. Cerebrovasc Brain Metab Rev 5:33–46PubMedGoogle Scholar
  48. 48.
    Takeshima T, Takao Y, Urakami K, Nishikawa S, Takahashi K (1989) Muscle contraction headache and migraine. Platelet activation and plasma norepinephrine during the cold pressor test. Cephalalgia 9:7–13. doi:10.1046/j.1468-2982.1989.0901007.x PubMedCrossRefGoogle Scholar
  49. 49.
    Tang Y, Anderson GM, Zabetian CP, Kohnke MD, Cubells JF (2005) Haplotype-controlled analysis of the association of a non-synonymous single nucleotide polymorphism at DBH (+ 1603C –> T) with plasma dopamine beta-hydroxylase activity. Am J Med Genet B Neuropsychiatr Genet 139:88–90. doi:10.1002/ajmg.b.30220 Google Scholar
  50. 50.
    Tang YL, Epstein MP, Anderson GM, Zabetian CP, Cubells JF (2007) Genotypic and haplotypic associations of the DBH gene with plasma dopamine beta-hydroxylase activity in African Americans. Eur J Hum Genet 15:878–883. doi:10.1038/sj.ejhg.5201838 PubMedCrossRefGoogle Scholar
  51. 51.
    Wei J, Ramchand CN, Hemmings GP (1997) Possible control of dopamine beta-hydroxylase via a codominant mechanism associated with the polymorphic (GT)n repeat at its gene locus in healthy individuals. Hum Genet 99:52–55. doi:10.1007/s004390050310 PubMedCrossRefGoogle Scholar
  52. 52.
    Weinshilboum RM (1978) Serum dopamine beta-hydroxylase. Pharmacol Rev 30:133–166PubMedGoogle Scholar
  53. 53.
    Zabetian CP, Anderson GM, Buxbaum SG, Elston RC, Ichinose H, Nagatsu T, Kim KS, Kim CH, Malison RT, Gelernter J, Cubells JF (2001) A quantitative-trait analysis of human plasma-dopamine beta-hydroxylase activity: evidence for a major functional polymorphism at the DBH locus. Am J Hum Genet 68:515–522. doi:10.1086/318198 PubMedCrossRefGoogle Scholar
  54. 54.
    Zabetian CP, Buxbaum SG, Elston RC, Kohnke MD, Anderson GM, Gelernter J, Cubells JF (2003) The structure of linkage disequilibrium at the DBH locus strongly influences the magnitude of association between diallelic markers and plasma dopamine beta-hydroxylase activity. Am J Hum Genet 72:1389–1400. doi:10.1086/375499 PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • F. Fernandez
    • 1
  • N. Colson
    • 1
  • S. Quinlan
    • 1
  • J. MacMillan
    • 2
  • R. A. Lea
    • 1
    • 3
  • L. R. Griffiths
    • 1
  1. 1.Genomics Research Centre, Griffith Institute for Health and Medical ResearchGriffith UniversityGold CoastAustralia
  2. 2.Queensland Clinical Genetics ServiceRoyal Children’s HospitalHerstonAustralia
  3. 3.Institute of Environmental Science and ResearchWellingtonNew Zealand

Personalised recommendations