GNAS1 T393C polymorphism is associated with migraine.
Migraineurs have an interictal sympathetic nervous system (SNS) hypofunctionality and hypersensitivity to adrenergic amines. The GNAS1 T393C polymorphism has been associated with a distinct SNS sensitivity in healthy subjects. We tested GNAS1 T393C variant in two independent sets of subjects. In the case-control subset, 365 migraine patients [194 with aura (MA)] vs. 347 healthy controls were studied. A significant excess of the CC genotype was found in migraneurs (31.2%) as opposed to controls (20.2%; P=0.003). Using a logistic regression model corrected for sex, the CC genotype conferred a general risk for migraine twice [odds ratio (OR) 1.79, 95% confidence interval (CI) 1.27-2.53; P=0.001] higher than CT/TT genotypes. Using parents from 117 migraine families, a marginally significant trend for association could be observed (P=0.025), but the transmission disequilibrium test for alleles maternally transmitted failed to demonstrate familial association. In this subgroup, CC genotype conferred a risk for migraine over twice (OR 2.20; 95% CI 1.14-4.40; P=0.019) higher than TT/TC genotypes. In conclusion, the GNAS1 T393C variant is associated with migraine, which suggests a genetic basis for its higher SNS sensitivity.
Oterino
A
A
Service of Neurology, University Hospital Marqués de Valdecilla (UC), Santander, Spain. aoterino@humv.es
Ruiz-Alegría
C
C
Castillo
J
J
Valle
N
N
Bravo
Y
Y
Cayón
A
A
Alonso
A
A
Tejera
P
P
Ruiz-Lavilla
N
N
Muñoz
P
P
Pascual
J
J
D000328:Adult; D002864:Chromogranins; D004252:DNA Mutational Analysis / Q000379:methods; D005260:Female; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics; D005820:Genetic Testing / Q000379:methods*; D014644:Genetic Variation / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D015994:Incidence; D008297:Male; D008881:Migraine Disorders / Q000201:enzymology* / Q000453:epidemiology* / Q000235:genetics; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D018570:Risk Assessment / Q000379:methods*; D012307:Risk Factors; D013030:Spain / Q000453:epidemiology
D002864:Chromogranins; C406732:GNAS protein, human; D019205:GTP-Binding Protein alpha Subunits, Gs