title: Genetic variants in the NOTCH4 gene influence the clinical features of migraine.
abstract: BACKGROUND
  Recent studies suggested an important role for vascular factors in migraine etiopathogenesis. Notch4 belongs to a family of transmembrane receptors that play an important role in vascular development and maintenance. The aim of this study was to test the hypothesis that polymorphisms of the NOTCH4 gene would modify the occurrence and the clinical features of migraine.
  
  
  RESULTS
  Using a case-control strategy, we genotyped 239 migraine patients and 264 controls for three different non-synonymous polymorphisms (T320A, G835V, R1346P) of the NOTCH4 gene and for the (CTG) n-encoding polyleucine polymorphism in exon 1. Although the analyzed polymorphisms resulted not associated with migraine, the clinical characteristics of our patients were significantly influenced by the different NOTCH4 genotypes. Longer duration of disease and severity of neurovegetative symptoms during headache attacks were associated with the R1346P and G835V polymorphisms, respectively. In female patients, worsening of migraine symptoms at menarche was significantly correlated with T320A polymorphism.
  
  
  CONCLUSIONS
  Our study shows that genetic variations within the NOTCH4 gene significantly modify the clinical characteristics of migraine and may have a role in disease pathogenesis.
authors.affiliation: Neurology II, Department of Neuroscience, University of Torino, Via Cherasco 15, Torino, 10126, Italy. elisa.rubino@unito.it
authors.forename: Elisa
authors.initials: E
authors.lastname: Rubino
authors.forename: Pierpaola
authors.initials: P
authors.lastname: Fenoglio
authors.forename: Salvatore
authors.initials: S
authors.lastname: Gallone
authors.forename: Flora
authors.initials: F
authors.lastname: Govone
authors.forename: Alessandro
authors.initials: A
authors.lastname: Vacca
authors.forename: Paola
authors.initials: P
authors.lastname: De Martino
authors.forename: Maria Laura
authors.initials: ML
authors.lastname: Giobbe
authors.forename: Silvia
authors.initials: S
authors.lastname: Boschi
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Pinessi
authors.forename: Salvatore
authors.initials: S
authors.lastname: Gentile
authors.forename: Innocenzo
authors.initials: I
authors.lastname: Rainero
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008297:Male; D008881:Migraine Disorders / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D000074562:Receptor, Notch4; D051880:Receptors, Notch / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C106075:NOTCH4 protein, human; D011518:Proto-Oncogene Proteins; D000074562:Receptor, Notch4; D051880:Receptors, Notch