title: Is SOD2 Ala16Val polymorphism associated with migraine with aura phenotype?
abstract: Several studies suggest a role of oxidative stress in the physiopathology of migraine, particularly in the form with aura. In a case-control study, we investigated the association between migraine and superoxide dismutase 1 (SOD1) and superoxide dismutase 2 (SOD2) genes in a cohort of 490 consecutive unrelated Caucasian migraineurs (migraine with aura [MwA], n=107; migraine without aura [MwoA], n=246; chronic migraine [CM], n=137) and 246 healthy controls recruited at our Headache and Pain Unit and stored in the Interinstitutional Multidisciplinary BioBank (BioBIM). Migraine phenotype was carefully detailed using face-to-face interviews. We examined polymorphisms of SOD1 gene (A/C substitution-rs2234694) and SOD2 gene (C/T transition-rs4880-Ala16Val). The rs4880 TT (Val/Val) genotype was associated (p=0.042) with the presence of unilateral cranial autonomic symptoms (UAs) in MwA patients. We also found a mild correlation between SOD2 rs4880 genotype and the type of acute migraine treatment (p=0.048) in MwA patients. Our findings suggest that SOD2 is a disease-modifier gene influencing oxidative mechanisms in MwA. These observations lead to the hypothesis that SOD2 polymorphism may cause a defective control of the oxidative phenomena linked to cortical spreading depression, the neurophysiological hallmark of migraine aura, causing an overstimulation of trigeminal neurons and UAs triggering.
authors.affiliation: 1 Interinstitutional Multidisciplinary Biobank (BioBIM), Biomarker Discovery and Advanced Technologies (BioDAT), IRCCS San Raffaele Pisana , Rome, Italy .
authors.forename: Raffaele
authors.initials: R
authors.lastname: Palmirotta
authors.forename: Piero
authors.initials: P
authors.lastname: Barbanti
authors.forename: Maria Laura
authors.initials: ML
authors.lastname: De Marchis
authors.forename: Gabriella
authors.initials: G
authors.lastname: Egeo
authors.forename: Cinzia
authors.initials: C
authors.lastname: Aurilia
authors.forename: Luisa
authors.initials: L
authors.lastname: Fofi
authors.forename: Cristiano
authors.initials: C
authors.lastname: Ialongo
authors.forename: Maria Giovanna
authors.initials: MG
authors.lastname: Valente
authors.forename: Patrizia
authors.initials: P
authors.lastname: Ferroni
authors.forename: David
authors.initials: D
authors.lastname: Della-Morte
authors.forename: Fiorella
authors.initials: F
authors.lastname: Guadagni
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D020325:Migraine with Aura / Q000201:enzymology / Q000235:genetics*; D020125:Mutation, Missense; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D013482:Superoxide Dismutase / Q000235:genetics*; D000099156:Superoxide Dismutase 2
chemical_list: D013482:Superoxide Dismutase; D000099156:Superoxide Dismutase 2