Abstract
BackgroundWe previously reported risk haplotypes for two genes related with serotonin and dopamine metabolism: MAOA in migraine without aura and DDC in migraine with aura. Herein we investigate the contribution to migraine susceptibility of eight additional genes involved in dopamine neurotransmission.MethodsWe performed a two-stage case-control association study of 50 tag single nucleotide polymorphisms (SNPs), selected according to genetic coverage parameters. The first analysis consisted of 263 patients and 274 controls and the replication study was composed by 259 cases and 287 controls. All cases were diagnosed according to ICHD-II criteria, were Spanish Caucasian, and were sex-matched with control subjects.ResultsSingle-marker analysis of the first population identified nominal associations of five genes with migraine. After applying a false discovery rate correction of 10%, the differences remained significant only for DRD2 (rs2283265) and TH (rs2070762). Multiple-marker analysis identified a five-marker T-C-G-C-G (rs12363125-rs2283265-rs2242592-rs1554929-rs2234689) risk haplotype in DRD2 and a two-marker A-C (rs6356-rs2070762) risk haplotype in TH that remained significant after correction by permutations. These results, however, were not replicated in the second independent cohort.ConclusionThe present study does not support the involvement of the DRD1, DRD2, DRD3, DRD5, DBH, COMT, SLC6A3 and TH genes in the genetic predisposition to migraine in the Spanish population.
Highlights
We previously reported risk haplotypes for two genes related with serotonin and dopamine metabolism: MAOA in migraine without aura and DDC in migraine with aura
In a previous study that evaluated the contribution of 19 serotonin-related genes to migraine susceptibility in our cohort of Spanish migraineurs, we reported risk haplotypes in MAOA for migraine without aura and in DDC for migraine with aura [10], both genes being key players in the serotonin and dopamine metabolic pathways
Fourteen single nucleotide polymorphism (SNP) were excluded from statistical analysis after data depuration in the first population: ten had genotype call rates 0.85, [see Additional File 1])
Summary
We previously reported risk haplotypes for two genes related with serotonin and dopamine metabolism: MAOA in migraine without aura and DDC in migraine with aura. We investigate the contribution to migraine susceptibility of eight additional genes involved in dopamine neurotransmission. Studies in animal models revealed that DA receptors are present in the trigeminovascular pathway and showed that DA can act as an inhibitor of nociceptive trigeminovascular transmission in the rat brain [6]. Along this line, DA antagonists have proved useful in aborting migraine headache or associated symptoms [5]. A review of pharmacological and therapeutic studies in migraine could not provide convincing evidence of a direct role of DA in migraine pathogenesis [8]
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