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MTHFR mutations cause arterial thrombosis and venous clots

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    by Katherine Kozlowski (Medical Writer)

    Mutations on the MTHFR gene disrupt the conversion of homocysteine to methionine in the presence of Vitamin B12 and folic acid; Therefore,  serum (blood) levels of Vitamin B12 and folic acid are inversely related to serum homocysteine levels.

    What does all this mean?  When vitamin B12 and folic acid levels are low, serum homocysteine levels are high.  

    Hyperhomocysteinemia, or high serum homocysteine levels, is a risk factor for vascular disease, both arterial and venous thrombosis.

    The proposed meechanisms by which hyperhomocysteinemia produces a prothrombotic effect incudes ipaired endothelial cell anticoagulant function, increasing procoagulant factors in the clotting cascade and inhibiting cofactors required for anticoagulant function.

    Overall, hyperhomocysteinemia is estimated to increase the risk for developing deep vein throimbosis 2.5 to 3 fold. 

    While there are several MTHFR polymorphisms, the common C677T polymorphism is a risk factor for hyperhomocysteinemia and thus several morbidities in patients with the MTHFR mutation.

    Siaw-Cheok et al (2015) investigated the MTHFR C677T polymorphism in its relationship to hyperhomocysteinemia and associated diseases including diabetes mellitus, cancers, and vascular diseases. Studies by Cai et al (2014) and Yang et al (2014) both reported the association between MTHFR C677T gene polymorphism and essential hypertension. Several studies reported increased association between the gene polymorphism and risk of stroke. “Forty percent of patients with coronary artery disease, cerebral, or peripheral artery disease were found to have high plasma homocysteine levels compared with only 15% in healthy individuals” (Welsch et al., 1997). The mechanism by which elevated serum homocysteine levels leads to vascular disease is unknown; however, Welsch et al (1997) suggests that atherogenesis (plaque formation) and thrombogenesis (blood clot formation) may be related to high homocysteine levels, and thus could lead to fibrosis (scarring) and muscle cell hyperplasia, stiffening and thickening arterial walls.

    Kang et al (1987) and Ubbink et al (1993) show that folic acid and vitamin B12 supplementation could normalize high serum levels of homocysteine. “Hyperhomocysteinemia is an emerging risk factor for various cardiovascular diseases and with the increasing significance of this polymorphism in view of the morbidity and mortality impact on the patients, further prevention strategies and nutritional recommendations with the supplementation of vitamin B12 and folic acid which reduces plasma homocysteine level would be necessary as part of future health education.” (Siaw-Cheok et al, 2015)

    Liew, S. C., & Gupta, E. D. (2015). Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism: epidemiology, metabolism and the associated diseases. European journal of medical genetics58(1), 1-10.