Testing for MTHFR – pro
Hypercoagulable states can be defined as a group of inherited or acquired conditions associated with a predisposition to venous thrombosis, arterial thrombosis, or both. Venous thromboembolic disease is the most common clinical manifestation resulting from hypercoagulable states. Among them is hyperhomocysteneimia. Inherited severe hyperhomocysteinemia (plasma level higher than 100 mmol/L), as seen in classic homocystinuria, may result from homozygous MTHFR or CBS deficiencies and, more rarely, from inherited errors of cobalamin (vitamin β12) metabolism. MTHFR and CBS deficiencie are not very common, ad clinical symptomst most commonly result from the C677T gene polymorphism, which is the most common mutation in the gene that codes for the MTHFR enzyme. Individuals who are heterozygous for the tlMTHFR variant have normal plasma homocysteine levels, whereas homozygous carriers may have mild to moderate fasting hyperhomocysteinemia in the setting of concomitant folate deficiency.
MTHFR polymorphism testing is frequently ordered by physicians as part of the clinical evaluation for thrombophilia. It was previously hypothesized that reduced enzyme activity of MTHFR led to mild hyperhomocysteinemia which led to an increased risk for venous thromboembolism, coronary heart disease, and recurrent pregnancy loss. Recent meta-analyses have disproven an association between hyperhomocysteinemia and risk for coronary heart disease and between MTHFR polymorphism status and risk for venous t-hromboembolism. There is growing evidence that MTHFR polymorphism testing has minimal clinical utility and, therefore should not be ordered as a part of a routine evaluation for thrombophilia.
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Hickey SE, Curry CJ, Toriello HV. ACMG Practice Guideline: lack of evidence for MTHFR polymorphism testing. Genet Med. 2013 Feb;15(2):153-6.
American College of Medical Genetics Practice Guidelines: Lack of Evidence for MTHFR Polymorphism Testing. Scott E. Hickey, M.D., FACMG, Cynthia J. Curry, M.D., FACMG and Helga V. Toriello, PhD, FACMG, Genetics in Medicine 2013:15(2):153-156
Colleen M. Johnson, MD Hypercoagulable States: A Review Vascular and Endovascular Surgery, Vol. 39, No. 2, 123-133 (2005)
U.S. Preventive Services Task Force (USPSTF). Using Nontraditional Risk Factors in Coronary Heart Disease Risk Assessment: U.S. Preventive Services Task Force Recommendation Statement. Ann Intern Med
October 6, 2009 vol. 151 no. 7 474-482.
TJOELLYN M. ABRAHAM, MD, LESLIE CHO, MD The homocysteine hypothesis: Still relevant to the prevention and treatment of cardiovascular disease? Cleveland Clinic Journal of Medicine December 2010 vol. 77 12 911-918
Seligsohn U, Lubetsky A. Genetic susceptibility to venous thrombosis. N Engl J Med. 2001;344:1222-1231.