title: Genotypes of the MTHFR C677T and MTRR A66G genes act independently to reduce migraine disability in response to vitamin supplementation.
abstract: BACKGROUND
  Migraine is a chronic disabling neurovascular condition that may in part be caused by endothelial and cerebrovascular disruption induced by hyperhomocysteinaemia. We have previously provided evidence indicating that reduction of homocysteine by vitamin supplementation can reduce the occurrence of migraine in women. The current study examined the genotypic effects of methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR) gene variants on the occurrence of migraine in response to vitamin supplementation.
  
  
  METHODS
  This was a 6-month randomized, double-blinded placebo-controlled trial of daily vitamin B supplementation (B(6), B(9) and B(12)) on reduction of homocysteine and of the occurrence of migraine in 206 female patients diagnosed with migraine with aura.
  
  
  RESULTS
  Vitamin supplementation significantly reduced homocysteine levels (P<0.001), severity of headache in migraine (P=0.017) and high migraine disability (P=0.022) in migraineurs compared with the placebo effect (P>0.1). When the vitamin-treated group was stratified by genotype, the C allele carriers of the MTHFR C677T variant showed a higher reduction in homocysteine levels (P<0.001), severity of pain in migraine (P=0.01) and percentage of high migraine disability (P=0.009) compared with those with the TT genotypes. Similarly, the A allele carriers of the MTRR A66G variants showed a higher level of reduction in homocysteine levels (P<0.001), severity of pain in migraine (P=0.002) and percentage of high migraine disability (P=0.006) compared with those with the GG genotypes. Genotypic analysis for both genes combined indicated that the treatment effect modification of the MTRR variant was independent of the MTHFR variant.
  
  
  CONCLUSIONS
  This provided further evidence that vitamin supplementation is effective in reducing migraine and also that both MTHFR and MTRR gene variants are acting independently to influence treatment response in female migraineurs.
authors.affiliation: Genomics Research Centre, Griffith Health Institute, Griffith University, Gold Coast, Queensland, Australia.
authors.forename: Saras
authors.initials: S
authors.lastname: Menon
authors.forename: Rod A
authors.initials: RA
authors.lastname: Lea
authors.forename: Bishakha
authors.initials: B
authors.lastname: Roy
authors.forename: Michelle
authors.initials: M
authors.lastname: Hanna
authors.forename: Shirley
authors.initials: S
authors.lastname: Wee
authors.forename: Larisa M
authors.initials: LM
authors.lastname: Haupt
authors.forename: Chris
authors.initials: C
authors.lastname: Oliver
authors.forename: Lyn R
authors.initials: LR
authors.lastname: Griffiths
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D019587:Dietary Supplements; D004311:Double-Blind Method; D005260:Female; D005287:Ferredoxin-NADP Reductase / Q000235:genetics*; D005492:Folic Acid / Q000008:administration & dosage; D005838:Genotype; D006801:Humans; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D020325:Migraine with Aura / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics; D015990:Placebo Effect; D014805:Vitamin B 12 / Q000008:administration & dosage; D025101:Vitamin B 6 / Q000008:administration & dosage; D014815:Vitamins / Q000008:administration & dosage*; D055815:Young Adult
chemical_list: D014815:Vitamins; D025101:Vitamin B 6; D005492:Folic Acid; C111241:methionine synthase reductase; D005287:Ferredoxin-NADP Reductase; C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D014805:Vitamin B 12