title: Two-stage case-control association study of dopamine-related genes and migraine.
abstract: BACKGROUND
  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. Herein we investigate the contribution to migraine susceptibility of eight additional genes involved in dopamine neurotransmission.
  
  
  METHODS
  We 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.
  
  
  RESULTS
  Single-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.
  
  
  CONCLUSIONS
  The 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.
authors.affiliation: Grup de Recerca en Neurologia Infantil, Hospital Universitari Vall d'Hebron, Barcelona, Spain. rcoromin@ir.vhebron.net
authors.forename: Roser
authors.initials: R
authors.lastname: Corominas
authors.forename: Marta
authors.initials: M
authors.lastname: Ribases
authors.forename: Montserrat
authors.initials: M
authors.lastname: Camiña
authors.forename: Ester
authors.initials: E
authors.lastname: Cuenca-León
authors.forename: Julio
authors.initials: J
authors.lastname: Pardo
authors.forename: Susana
authors.initials: S
authors.lastname: Boronat
authors.forename: María-Jesús
authors.initials: MJ
authors.lastname: Sobrido
authors.forename: Bru
authors.initials: B
authors.lastname: Cormand
authors.forename: Alfons
authors.initials: A
authors.lastname: Macaya
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D016022:Case-Control Studies; D004298:Dopamine / Q000235:genetics*; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D008881:Migraine Disorders / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011954:Receptors, Dopamine / Q000235:genetics*; D013030:Spain; D055815:Young Adult
chemical_list: D005819:Genetic Markers; D011954:Receptors, Dopamine; D004298:Dopamine