title: Haplotype analysis of the folate-related genes MTHFR, MTRR, and MTR and migraine with aura.
abstract: OBJECTIVE
  The C677T variant in the methylenetetrahydrofolate reductase ( MTHFR ; EC 1.5.1.20) enzyme, a key player in the folate metabolic pathway, has been associated with increased risk of migraine with aura. Other genes encoding molecular components of this pathway include methionine synthase ( MTR ; EC 2.1.1.13) and methionine synthase reductase ( MTRR ; EC 2.1.1.135) among others. We performed a haplotype analysis of migraine risk and MTHFR , MTR , and MTRR .
  
  
  METHODS
  Study participants are from a random sub-sample participating in the population-based AGES-Reykjavik Study, including subjects with non-migraine headache ( N = 367), migraine without aura ( N = 85), migraine with aura ( N = 167), and no headache ( N = 1347). Haplotypes spanning each gene were constructed using Haploview. Association testing was performed on single SNP and haplotypes using logistic regression, controlling for demographic and cardiovascular risk factors and correcting for multiple testing.
  
  
  RESULTS
  Haplotype analysis suggested an association between MTRR haplotypes and reduced risk of migraine with aura. All other associations were not significant after correcting for multiple testing.
  
  
  CONCLUSIONS
  These results suggest that MTRR variants may protect against migraine with aura in an older population.
authors: Department of Psychology, Center for the Neural Basis of Cognition, University of Pittsburgh, Pittsburgh, PA 15260, USA. kroecklein@gmail.com
authors: Kathryn A
authors: KA
authors: Roecklein
authors: Ann I
authors: AI
authors: Scher
authors: Albert
authors: A
authors: Smith
authors: Tamara
authors: T
authors: Harris
authors: Gudny
authors: G
authors: Eiriksdottir
authors: Melissa
authors: M
authors: Garcia
authors: Villi
authors: V
authors: Gudnason
authors: Lenore J
authors: LJ
authors: Launer
mesh_terms: D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005287:Ferredoxin-NADP Reductase / Q000235:genetics*; D005492:Folic Acid / Q000235:genetics*; D056726:Genetic Association Studies / Q000379:methods; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D007055:Iceland / Q000453:epidemiology; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D020325:Migraine with Aura / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics
chemical_list: D005492:Folic Acid; C111241:methionine synthase reductase; D005287:Ferredoxin-NADP Reductase; C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase