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Methylenetetrahydrofolate Reductase Gene Variant (MTHFR C677T) and Migraine: A Case Control Study and Meta-analysis

Zainab Samaan1*, Daria Gaysina2, Sarah Cohen-Woods2, Nick Craddock3, Lisa Jones4, Ania Korszun5, Mike Owen3, Andrew Mente6, Peter McGuffin2 and Anne Farmer2

Author Affiliations

1 Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, ON, Canada

2 Medical Research Council (MRC) Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, London, UK

3 Department of Psychological Medicine, School of Medicine, Cardiff University, Cardiff, UK

4 Division of Neuroscience, University of Birmingham, Birmingham, UK

5 Barts and The London, Queen Mary's School of Medicine and Dentistry, London, UK

6 Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, ON, Canada

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BMC Neurology 2011, 11:66  doi:10.1186/1471-2377-11-66

Published: 2 June 2011



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.


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.


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).


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.