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Association between migraine and a functional polymorphism at the DBH locus

Journal 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 caseâÂÂcontrol cohorts. These two markers are putative functional SNPs, one within the promoter (âÂÂ1021CâÂÂT) and another SNP (+1603CâÂÂT) 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 (PâÂÂ¥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.

Authors


  •   Fernandez-Enright, Francesca E.
  •   Colson, Natalie J. (external author)
  •   Quinlan, S. (external author)
  •   MacMillan, John (external author)
  •   Lea, Rod A. (external author)
  •   Griffiths, Lyn R. (external author)

Publication Date


  • 2009

Citation


  • Fernandez, F., Colson, N., Quinlan, S., MacMillan, J., Lea, R. A. & Griffiths, L. R. (2009). Association between migraine and a functional polymorphism at the DBH locus. Neurogenetics, 10 (3), 199-208.

Scopus Eid


  • 2-s2.0-70249118588

Ro Metadata Url


  • http://ro.uow.edu.au/hbspapers/1726

Has Global Citation Frequency


Number Of Pages


  • 9

Start Page


  • 199

End Page


  • 208

Volume


  • 10

Issue


  • 3

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 caseâÂÂcontrol cohorts. These two markers are putative functional SNPs, one within the promoter (âÂÂ1021CâÂÂT) and another SNP (+1603CâÂÂT) 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 (PâÂÂ¥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.

Authors


  •   Fernandez-Enright, Francesca E.
  •   Colson, Natalie J. (external author)
  •   Quinlan, S. (external author)
  •   MacMillan, John (external author)
  •   Lea, Rod A. (external author)
  •   Griffiths, Lyn R. (external author)

Publication Date


  • 2009

Citation


  • Fernandez, F., Colson, N., Quinlan, S., MacMillan, J., Lea, R. A. & Griffiths, L. R. (2009). Association between migraine and a functional polymorphism at the DBH locus. Neurogenetics, 10 (3), 199-208.

Scopus Eid


  • 2-s2.0-70249118588

Ro Metadata Url


  • http://ro.uow.edu.au/hbspapers/1726

Has Global Citation Frequency


Number Of Pages


  • 9

Start Page


  • 199

End Page


  • 208

Volume


  • 10

Issue


  • 3