title: Methylenetetrahydrofolate reductase gene variant (MTHFR C677T) and migraine: a case control study and meta-analysis.
abstract: BACKGROUND
  Migraine is a common disorder that often coexists with depression. While a functional polymorphism in methyleneterahydrofolate reductase gene (MTHFR C677T) has been implicated in depression; the evidence to support an association of MTHFR with migraine has been inconclusive. We aim to investigate the effect of this variant on propensity for migraine and to perform a systematic review and meta-analysis of studies of MTHFR and migraine to date.
  
  
  METHODS
  Individuals with migraine (n = 447) were selected from the Depression Case Control (DeCC) study to investigate the association between migraine and MTHFR C677T single nucleotide polymorphism (SNP) rs1801133 using an additive model compared to non-migraineurs adjusting for depression status. A meta-analysis was performed and included 15 studies of MTHFR and migraine.
  
  
  RESULTS
  MTHFR C677T polymorphism was associated with migraine with aura (MA) (OR 1.31, 95% CI 1.01-1.70, p = 0.039) that remained significant after adjusting for age, sex and depression status. A meta-analysis of 15 case-control studies showed that T allele homozygosity is significantly associated with MA (OR = 1.42; 95% CI, 1.10-1.82) and total migraine (OR = 1.37; 95% CI, 1.07-1.76), but not migraine without aura (OR = 1.16; 95% CI, 0.36-3.76). In studies of non-Caucasian population, the TT genotype was associated with total migraine (OR= 3.46; 95% CI, 1.22-9.82), whereas in studies of Caucasians this variant was associated with MA only (OR = 1.28; 95% CI, 1.002-1.63).
  
  
  CONCLUSIONS
  MTHFR C677T is associated with MA in individuals selected for depression study. A meta-analysis of 15 studies supports this association and demonstrated effects across ethnic groups.
authors.affiliation: Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, ON, Canada. samaanz@mcmaster.ca
authors.forename: Zainab
authors.initials: Z
authors.lastname: Samaan
authors.forename: Daria
authors.initials: D
authors.lastname: Gaysina
authors.forename: Sarah
authors.initials: S
authors.lastname: Cohen-Woods
authors.forename: Nick
authors.initials: N
authors.lastname: Craddock
authors.forename: Lisa
authors.initials: L
authors.lastname: Jones
authors.forename: Ania
authors.initials: A
authors.lastname: Korszun
authors.forename: Mike
authors.initials: M
authors.lastname: Owen
authors.forename: Andrew
authors.initials: A
authors.lastname: Mente
authors.forename: Peter
authors.initials: P
authors.lastname: McGuffin
authors.forename: Anne
authors.initials: A
authors.lastname: Farmer
mesh_terms: D000328:Adult; D019731:Carbon-Nitrogen Ligases / Q000235:genetics*; D016022:Case-Control Studies; D004252:DNA Mutational Analysis; D003863:Depression / Q000175:diagnosis / Q000209:etiology; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D008297:Male; D015201:Meta-Analysis as Topic; D008875:Middle Aged; D020325:Migraine with Aura / Q000150:complications / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011569:Psychiatric Status Rating Scales
chemical_list: D019731:Carbon-Nitrogen Ligases; C021557:5,10-methenyltetrahydrofolate synthetase