Skip to main content

Association analysis of chromosome 1 migraine candidate genes

Journal Article


Download full-text (Open Access)

Abstract


  • Background

    Migraine with aura (MA) is a subtype of typical migraine. Migraine with aura (MA) also encompasses a rare severe subtype Familial Hemiplegic Migraine (FHM) with several known genetic loci. The type 2 FHM (FHM-2) susceptibility locus maps to chromosome 1q23 and mutations in the ATP1A2 gene at this site have recently been implicated. We have previously provided evidence of linkage of typical migraine (predominantly MA) to microsatellite markers on chromosome 1, in the 1q31 and 1q23 regions. In this study, we have undertaken a large genomic investigation involving candidate genes that lie within the chromosome 1q23 and 1q31 regions using an association analysis approach.

    Methods

    We have genotyped a large population of case-controls (243 unrelated Caucasian migraineurs versus 243 controls) examining a set of 5 single nucleotide polymorphisms (SNPs) and the Fas Ligand dinucleotide repeat marker, located within the chromosome 1q23 and 1q31 regions.

    Results

    Several genes have been studied including membrane protein (ATP 1 subtype A4 and FasL), cytoplasmic glycoprotein (CASQ 1) genes and potassium (KCN J9 and KCN J10) and calcium (CACNA1E) channel genes in 243 migraineurs (including 85% MA and 15% of migraine without aura (MO)) and 243 matched controls. After correction for multiple testing, chi-square results showed non-significant P values (P > 0.008) across all SNPs (and a CA repeat) tested in these different genes, however results with the KCN J10 marker gave interesting results (P = 0.02) that may be worth exploring further in other populations.

    Conclusion

    These results do not show a significant role for the tested candidate gene variants and also do not support the hypothesis that a common chromosome 1 defective gene influences both FHM and the more common forms of migraine.

Authors


  •   Fernandez-Enright, Francesca E.
  •   Curtain, Robert P.. (external author)
  •   Colson, Natalie J. (external author)
  •   Ovcaric, Micky (external author)
  •   MacMillan, John (external author)
  •   Griffiths, Lyn R. (external author)

Publication Date


  • 2007

Citation


  • Fernandez, F., Curtain, R. P., Colson, N. J., Ovcaric, M., MacMillan, J. & Griffiths, L. R. (2007). Association analysis of chromosome 1 migraine candidate genes. BMC Medical Genetics, 8 (57), 1-8.

Scopus Eid


  • 2-s2.0-35348879616

Ro Full-text Url


  • http://ro.uow.edu.au/cgi/viewcontent.cgi?article=1918&context=sspapers

Ro Metadata Url


  • http://ro.uow.edu.au/sspapers/919

Has Global Citation Frequency


Number Of Pages


  • 7

Start Page


  • 1

End Page


  • 8

Volume


  • 8

Issue


  • 57

Place Of Publication


  • United Kingdom

Abstract


  • Background

    Migraine with aura (MA) is a subtype of typical migraine. Migraine with aura (MA) also encompasses a rare severe subtype Familial Hemiplegic Migraine (FHM) with several known genetic loci. The type 2 FHM (FHM-2) susceptibility locus maps to chromosome 1q23 and mutations in the ATP1A2 gene at this site have recently been implicated. We have previously provided evidence of linkage of typical migraine (predominantly MA) to microsatellite markers on chromosome 1, in the 1q31 and 1q23 regions. In this study, we have undertaken a large genomic investigation involving candidate genes that lie within the chromosome 1q23 and 1q31 regions using an association analysis approach.

    Methods

    We have genotyped a large population of case-controls (243 unrelated Caucasian migraineurs versus 243 controls) examining a set of 5 single nucleotide polymorphisms (SNPs) and the Fas Ligand dinucleotide repeat marker, located within the chromosome 1q23 and 1q31 regions.

    Results

    Several genes have been studied including membrane protein (ATP 1 subtype A4 and FasL), cytoplasmic glycoprotein (CASQ 1) genes and potassium (KCN J9 and KCN J10) and calcium (CACNA1E) channel genes in 243 migraineurs (including 85% MA and 15% of migraine without aura (MO)) and 243 matched controls. After correction for multiple testing, chi-square results showed non-significant P values (P > 0.008) across all SNPs (and a CA repeat) tested in these different genes, however results with the KCN J10 marker gave interesting results (P = 0.02) that may be worth exploring further in other populations.

    Conclusion

    These results do not show a significant role for the tested candidate gene variants and also do not support the hypothesis that a common chromosome 1 defective gene influences both FHM and the more common forms of migraine.

Authors


  •   Fernandez-Enright, Francesca E.
  •   Curtain, Robert P.. (external author)
  •   Colson, Natalie J. (external author)
  •   Ovcaric, Micky (external author)
  •   MacMillan, John (external author)
  •   Griffiths, Lyn R. (external author)

Publication Date


  • 2007

Citation


  • Fernandez, F., Curtain, R. P., Colson, N. J., Ovcaric, M., MacMillan, J. & Griffiths, L. R. (2007). Association analysis of chromosome 1 migraine candidate genes. BMC Medical Genetics, 8 (57), 1-8.

Scopus Eid


  • 2-s2.0-35348879616

Ro Full-text Url


  • http://ro.uow.edu.au/cgi/viewcontent.cgi?article=1918&context=sspapers

Ro Metadata Url


  • http://ro.uow.edu.au/sspapers/919

Has Global Citation Frequency


Number Of Pages


  • 7

Start Page


  • 1

End Page


  • 8

Volume


  • 8

Issue


  • 57

Place Of Publication


  • United Kingdom