Two-stage case-control association study of dopamine-related genes and migraine.
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.
Corominas
Roser
R
Grup de Recerca en Neurologia Infantil, Hospital Universitari Vall d'Hebron, Barcelona, Spain. rcoromin@ir.vhebron.net
Ribases
Marta
M
Camiña
Montserrat
M
Cuenca-León
Ester
E
Pardo
Julio
J
Boronat
Susana
S
Sobrido
María-Jesús
MJ
Cormand
Bru
B
Macaya
Alfons
A
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
D005819:Genetic Markers; D011954:Receptors, Dopamine; D004298:Dopamine