AbstractBackgroundWe previously reported risk haplotypes for two genes related with serotonin and dopamine metabolism:MAOAin migraine without aura andDDCin 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 forDRD2(rs2283265) andTH(rs2070762). Multiple-marker analysis identified a five-marker T-C-G-C-G (rs12363125-rs2283265-rs2242592-rs1554929-rs2234689) risk haplotype inDRD2and a two-marker A-C (rs6356-rs2070762) risk haplotype inTHthat 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 theDRD1,DRD2,DRD3,DRD5,DBH,COMT,SLC6A3andTHgenes in the genetic predisposition to migraine in the Spanish population.