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Analysis of the MTHFR C677T variant with migraine phenotypes

Annie Liu1, Saraswathy Menon1, Natalie J Colson1, Sharon Quinlan1, Hannah Cox1, Madelyn Peterson2, Thomas Tiang1, Larisa M Haupt1, Rod A Lea13 and Lyn R Griffiths1*

Author Affiliations

1 Genomics Research Centre, School of Medical Science, Griffith University Gold Coast, PMB 50, Gold Coast Mail Centre, Queensland, Australia, 9726

2 School of Biomolecular & Biomedical Science, Griffith University, Nathan, Queensland, Australia

3 Institute of Environmental Science and Research, 34 Kenepuru Drive, Porirua Wellington, New Zealand

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BMC Research Notes 2010, 3:213  doi:10.1186/1756-0500-3-213

Published: 28 July 2010



The methylenetetrahydrofolate reductase (MTHFR) gene variant C677T has been implicated as a genetic risk factor in migraine susceptibility, particularly in Migraine with Aura. Migraine, with and without aura (MA and MO) have many diagnostic characteristics in common. It is postulated that migraine symptomatic characteristics might themselves be influenced by MTHFR. Here we analysed the clinical profile, migraine symptoms, triggers and treatments of 267 migraineurs previously genotyped for the MTHFR C677T variant. The chi-square test was used to analyse all potential relationships between genotype and migraine clinical variables. Regression analyses were performed to assess the association of C677T with all migraine clinical variables after adjusting for gender.


The homozygous TT genotype was significantly associated with MA (P < 0.0001) and unilateral head pain (P = 0.002). While the CT genotype was significantly associated with physical activity discomfort (P < 0.001) and stress as a migraine trigger (P = 0.002). Females with the TT genotype were significantly associated with unilateral head pain (P < 0.001) and females with the CT genotype were significantly associated with nausea (P < 0.001), osmophobia (P = 0.002), and the use of natural remedy for migraine treatment (P = 0.003). Conversely, male migraineurs with the TT genotype experienced higher incidences of bilateral head pain (63% vs 34%) and were less likely to use a natural remedy as a migraine treatment compared to female migraineurs (5% vs 20%).


MTHFR genotype is associated with specific clinical variables of migraine including unilateral head pain, physical activity discomfort and stress.