Migraine and MTHFR C677T genotype in a population-based sample

Authors

  • Ann I. Scher PhD,

    Corresponding author
    1. Department of Preventive Medicine and Biometrics, Uniformed Services University, Bethesda, MD
    2. Laboratory of Epidemiology, Demography, and Biometry, National Institute on Aging, National Institutes of Health, Bethesda, MD
    • Uniformed Services University, Department of Preventive Medicine and Biometrics, 4301 Jones Bridge Road; Bethesda, MD 20814-4799
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  • Gisela M. Terwindt MD, PhD,

    1. Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands
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  • W. M. Monique Verschuren PhD,

    1. Centre for Prevention and Health Services Research, National Institute of Public Health and the Environment, Bilthoven, The Netherlands
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  • Mark C. Kruit MD,

    1. Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands
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  • Henk J. Blom PhD,

    1. Laboratory of Pediatrics and Neurology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, The Netherlands
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  • Hisanori Kowa MD, PhD,

    1. Department of Neurology, Institute of Neurological Sciences, Faculty of Medicine, Tottori University, Yonago, Japan
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  • Rune R. Frants PhD,

    1. Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands
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  • Arn M. J. M. van den Maagdenberg PhD,

    1. Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands
    2. Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands
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  • Mark van Buchem MD, PhD,

    1. Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands
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  • Michel D. Ferrari MD, PhD,

    1. Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands
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  • Lenore J. Launer PhD

    1. Laboratory of Epidemiology, Demography, and Biometry, National Institute on Aging, National Institutes of Health, Bethesda, MD
    2. Centre for Prevention and Health Services Research, National Institute of Public Health and the Environment, Bilthoven, The Netherlands
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Abstract

Objective

Migraine with aura is associated with increased risk of stroke. The MTHFR C677T genotype has been associated with increased risk of migraine in selected clinical samples and with elevated homocysteine, a risk factor for stroke. We assessed the association of the MTHFR C677T variant with migraine and the mediating effect of cardiovascular risk factors and metabolic markers of genotype status.

Methods

We compared adult migraineurs with aura (MA; n = 187), without aura (MO; n = 226), and nonmigraineurs (n = 1,212) from the population-based Genetic Epidemiology of Migraine study.

Results

Compared with the wild-type genotype, the T/T genotype was associated with increased odds of MA (odds ratio [OR], 2.05; 95% confidence interval, 1.2–3.4; p < 0.006), with a trend of increasing numbers of T alleles (OR, 1.40; 95% confidence interval, 1.1–1.8; p < 0.007). ORs were slightly attenuated after adjusting for homocysteine.

Interpretation

Risk of MA is associated with MTHFR C674T homozygosity, independent of other cardiovascular risk factors. Ann Neurol 2006

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