Abstract for presentation at 11th International Congress of Human Genetics

Association between a 19bp deletion polymorphism at the dopamine ß-hydroxylase locus and migraine with aura

  • Dr Francesca Fernandez, Genomics Research Centre, School of Health Science, Griffith University, Gold Coast, Queensland, Australia
  • Ms Natalie Colson, Genomics Research Centre, School of Health Science, Griffith University, Gold Coast, Queensland, Australia
  • Ms Claire Bellis, Genomics Research Centre, School of Health Science, Griffith University, Gold Coast, Queensland, Australia
  • Dr Rod Lea, Environmental Science and Research, Wellington, New Zealand
  • Pr Lyn Griffiths, Genomics Research Centre, School of Health Science, Griffith University, Gold Coast, Queensland, Australia

    • Migraine is a debilitating neurological disorder characterised by recurrent attacks of severe headache. The disorder is highly prevalent, affecting approximately 12% of Caucasian populations. It is well known that migraine has a strong genetic component, although the type and number of genes involved is not yet clear; however there is evidence to suggest that dopamine related genes may be involved in the pathogenesis of migraine. Our previous work has investigated dopamine related migraine candidate genes and has reported a significant allelic association with migraine of a microsatellite (STR) localised to the promoter region of the dopamine beta-hydroxylase (DBH) gene. The present study performed an association analysis in a larger population of case-controls and examined two genetic DBH polymorphisms (a functional insertion/deletion promoter and coding SNP A444G polymorphisms). These were genotyped in 275 unrelated Caucasian migraineurs and 275 control individuals. Although no any significant association have been found for STR and SNP polymorphisms, the results showed a significant association between the homozygous deletion genotype and the disease (X²= 8.92, 2df, P= 0.011), in particular in migraine with aura (X² = 11.53, P=0.003) compared to control group. Furthermore, the analysis of the difference in insertion/deletion polymorphism stratified by gender revealed that male individuals with the homozygote deletion genotype had three times the risk to develop migraine (OR=3.67, 95% Cl 1.36-9.88), compared to the female group (OR=1.41, 95% Cl 0.86-2.3). This polymorphism has functional consequences resulting in decrease of activity of the DBH enzyme, which may explain its potential role in a susceptibility to migraine. It is also in linkage disequilibrium with the previously reported associated with DBH microsatellite.

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