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Archived Comments for: The methylenetetrahydrofolate reductase gene variant C677T influences susceptibility to migraine with aura

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  1. Endothelial Cells lack CBS and make the MTHFR arm more important in controlling Homocysteine levels and eNOS eNO function within the endothelial cell

    Melvin Hayden, Department of Family and Community Medicine University of Missouri School of Medicine

    12 February 2004

    Congratulations on an exciting, well planned and very well written study of this exciting field of study.

    Since endothelial cells (Ec) lack Cystathionine Beta Synthase the MTHFR enzyme assumes a greater role in controling homocysteine levels.

    We have proposed a FOLATE SHUTTLE phenomenon, whereby, 5MTHF (FOLIC ACID) is preferentially shuttled to provide electrons and hydrogen (as FOIC ACID is not only a methyl donor but also a hydrogen and electron donor) to the tetrahydrobiopterin (BH4) requisite co-factor for the eNOS enzyme to run the eNOS reaction to produce endothelial nitric oxide (eNO).

    As folate is preferentially shuttled into the eNOS reaction its substrate will be decreased to run the folate-methionine cycle and therefore the levels of Hcy would reflect the underlying increased demand for folate in states of oxidative stress in order to run the eNOS reaction and compensate the biological system to produce more eNO in a state of eNO relative deficiency.

    This folate shuttle, then combined with the relative dysfunction of the MTHFR enzyme due to a misspelling (MTHFR C667T or TT genotype) would only add to the increasing levels of Hcy.

    We currently feel that Hcy is a reflection of underlying oxidative-redox stress to the endothelial cell.

    Thank you and your group for such a wonderful paper in helping to understand the role of this gene polymophism as it more prevalent and associated with more clinical disease of the vasculature than previously recognized.

    Homocysteine is definitely a major player in cardiovascular and neurovascular disease. Incidently, have you any information regarding folate supplementation and the decrease in the frequency of the migrain syndrome. Over the years we have noted an improvement clinically, however we have not done any trials to prove this.


    M.R. Hayden, M.D.

    Adjunct Assistant Professor

    Department of Family and Community Medicine

    University of Missouri

    Competing interests