Association analysis of chromosome 1 migraine candidate genes.
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.


CONCLUSIONS
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.
Fernandez
Francesca
F
Genomics Research Centre, School of Health Science, Griffith University, Gold Coast, Queensland, Australia. f.fernandez@griffith.edu.au
Curtain
Robert P
RP
Colson
Natalie J
NJ
Ovcaric
Micky
M
MacMillan
John
J
Griffiths
Lyn R
LR
D000483:Alleles; D002874:Chromosome Mapping; D002878:Chromosomes, Human, Pair 1; D003430:Cross-Sectional Studies; D005787:Gene Frequency; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D020325:Migraine with Aura / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide
D005819:Genetic Markers