title: Influence of MTHFR genotype on contingent negative variation and MRI abnormalities in migraine.
abstract: BACKGROUND
  The MTHFR C677T genotype has been associated with increased risk of migraine, particularly of migraine with aura (MA) in selected clinical samples and with elevated homocysteine. The hyper-homocysteinemia may favor the vascular and neuronal mechanism underlying migraine, and the risk of stroke.
  
  
  OBJECTIVE
  The first aim of the present study was to examine the Contingent Negative Variation (CNV) amplitude and habituation pattern in a migraine sample versus non-migraine subjects, at the light of the MTHFR genotype, according to an unrelated and clinical based case-control panel. The second aim was to compare the frequency of Magnetic Resonance Imaging (MRI) subclinical brain lesions across the different C677 genotypes in the same migraine sample, selected for the young age and the absence of any cardiovascular risk factor.
  
  
  METHODS
  One hundred and five 18-45 year old out-patients, 90 affected by migraine without aura (MO) and 15 by MA, and 97 non-migraine healthy subjects, age and sex matched, were selected for the genetic analysis. All subjects had a common ethnic origin from Puglia. Sixty-four migraine subjects and 33 control subjects were submitted to the recording of the CNV. All migraine subjects underwent the MRI evaluation.
  
  
  RESULTS
  The frequency of homozygosis was 14.33% in normal subjects, versus 25.7% in MA + MO group (chi2-test: 10.80 P= .001). The frequency of homozygosis in MO patients, was 25.5% (MA versus N: chi2-test: 9 P= .003), in MA group it was 26.6%. Considering the MTHFR genotype in migraine patients and controls, the C677TT subjects exhibited a reduced habituation index of the early CNV (iCNV), in respect with both C677TC and C677CC; in the migraine group, there was a significant decrease of CNV habituation in patients with homozygosis and a positive correlation between the habituation index values and the homocysteine levels. Nineteen migraine patients exhibited subclinical brain lesions (18.05%): patients with C677T homozygosis did not exhibit a higher risk for MRI abnormalities.
  
  
  CONCLUSIONS
  This unrelated and clinical based case-control study showed that genetically induced hyper-homocysteinemia may favor the neuronal factors predisposing to migraine, while it does not influence the presence of subclinical vascular brain lesions probably linked with increased risk of stroke.
authors.affiliation: Neurologic and Psychiatric Sciences, Neurological Clinical Section, University of Bari, Italy.
authors.forename: Marina
authors.initials: M
authors.lastname: de Tommaso
authors.forename: Olimpia
authors.initials: O
authors.lastname: Difruscolo
authors.forename: Michele
authors.initials: M
authors.lastname: Sardaro
authors.forename: Luciana
authors.initials: L
authors.lastname: Losito
authors.forename: Claudia
authors.initials: C
authors.lastname: Serpino
authors.forename: Anna
authors.initials: A
authors.lastname: Pietrapertosa
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Santeramo
authors.forename: Franca
authors.initials: F
authors.lastname: Dicuonzo
authors.forename: Aristide
authors.initials: A
authors.lastname: Carella
authors.forename: Paolo
authors.initials: P
authors.lastname: Lamberti
authors.forename: Paolo
authors.initials: P
authors.lastname: Livrea
mesh_terms: D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D003265:Contingent Negative Variation / Q000235:genetics* / Q000502:physiology; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006710:Homocysteine / Q000097:blood; D006720:Homozygote; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D008881:Migraine Disorders / Q000235:genetics* / Q000473:pathology*; D012307:Risk Factors; D020521:Stroke / Q000209:etiology
chemical_list: D006710:Homocysteine; D042965:Methylenetetrahydrofolate Reductase (NADPH2)