At a Glance
Why Get Tested?
When to Get Tested?
When you have elevated homocysteine levels; sometimes when a close relative has MTHFR gene mutations or has developed CVD or thrombosis at an early age
A blood sample drawn from a vein in your arm
Test Preparation Needed?
The Test Sample
What is being tested?
The methylenetetrahydrofolate reductase (MTHFR) gene oversees the production of the MTHFR enzyme. This enzyme changes one form of folate into another and is part of the process that converts homocysteine into methionine, an important building block for many proteins.
MTHFR testing detects two relatively common DNA sequence variants (single nucleotide polymorphisms, SNPs) in the MTHFR gene, C677T and A1298C. These SNPs result in changes in the DNA (or mutations) and are associated with increased homocysteine levels in the blood, which may increase the risk of premature cardiovascular disease (CVD), thrombosis, and stroke. Approximately 10-12% of the North American population is homozygous for C677T. There is some ethnic variability in the frequency, with the highest being in those of Mediterranean ancestry and the lowest in those of African ancestry.
The C677T variant results in a less active form of the MTHFR enzyme. When a person has two copies of the MTHFR C677T gene mutation (homozygous) or one copy of MTHFR C677T and one copy of A1298C (compound heterozygous), decreased MTHFR enzyme activity slows down the homocysteine-to-methionine conversion process and can lead to a buildup of homocysteine in the blood.
The increase in homocysteine is often mild to moderate but will vary from person to person depending upon the amount MTHFR enzyme activity. Homocysteine buildup is worsened when the affected person is folate-deficient.
Results of some studies suggest that high levels of homocysteine in the blood may contribute to risk of CVD by damaging blood vessel walls and promoting formation of plaque (atherosclerosis) and inappropriate blood clots (thrombosis). However, a direct link between homocysteine levels and CVD or thrombotic risk has not been proven. For more on this, see the article on Homocysteine.
How is the sample collected for testing?
A blood sample is obtained by inserting a needle into a vein in the arm.
NOTE: If undergoing medical tests makes you or someone you care for anxious, embarrassed, or even difficult to manage, you might consider reading one or more of the following articles: Coping with Test Pain, Discomfort, and Anxiety, Tips on Blood Testing, Tips to Help Children through Their Medical Tests, and Tips to Help the Elderly through Their Medical Tests.
Another article, Follow That Sample, provides a glimpse at the collection and processing of a blood sample and throat culture.
Is any test preparation needed to ensure the quality of the sample?
No test preparation is needed.
Ask a Laboratory Scientist
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NOTE: This article is based on research that utilizes the sources cited here as well as the collective experience of the Lab Tests Online Editorial Review Board. This article is periodically reviewed by the Editorial Board and may be updated as a result of the review. Any new sources cited will be added to the list and distinguished from the original sources used.
Mandava, P, et. al. (Updated 2009 May 25). Metabolic Disease and Stroke - Homocystinuria/Homocysteinemia. eMedicine [On-line information]. Available online at http://emedicine.medscape.com/article/1162007-overview through http://emedicine.medscape.com. Accessed October 2010.
(Reviewed 2008 January). MTHFR. Genetics Home Reference [On-line information]. Available online at http://ghr.nlm.nih.gov/gene/MTHFR through http://ghr.nlm.nih.gov. Accessed October 2010.
Fong, C. (Revised 2010 February). Amino Acid and Organic Acid Metabolism Disorders. Merck Manual for Healthcare Professionals [On-line information]. Available online at http://www.merck.com/mmpe/sec19/ch296/ch296c.html?qt=MTHFR&alt=sh through http://www.merck.com . Accessed October 2010.
Hart, K. et. al. (Updated 2010 August). Hypercoagulable States – Thrombophilia. ARUP Consult [On-line information]. Available online at http://www.arupconsult.com/Topics/Thrombophilia.html?client_ID=LTD through http://www.arupconsult.com. Accessed October 2010.
(© 1995-2010). MayoClinic Mayo Medical Laboratories. Unit Code 91457: Methylenetetrahydrofolate Reductase (MTHFR) 2 Mutations [On-line information]. Available online at http://www.mayomedicallaboratories.com/test-catalog/Overview/91457 through http://www.mayomedicallaboratories.com. Accessed October 2010.
(© 2006-2010). Methylenetetrahydrofolate Reductase (MTHFR) 2 Mutations: 0055655. ARUP's Laboratory Test Directory [On-line information]. Available online at http://www.aruplab.com/guides/ug/tests/0055655.jsp through http://www.aruplab.com. Accessed October 2010.
Varga, E. et. al. (2005 May 17). Homocysteine and MTHFR Mutations, Relation to Thrombosis and Coronary Artery Disease. Circulation. 2005;111:e289-e293 [On-line information]. Available online at http://circ.ahajournals.org/cgi/content/full/111/19/e289 through http://circ.ahajournals.org. Accessed October 2010.
Curtin, K. et. al. (2004 February). MTHFR C677T and A1298C Polymorphisms. Cancer Epidemiology, Biomarkers & Prevention. February 1, 2004 13; 285 [On-line information]. Available online at http://cebp.aacrjournals.org/content/13/2/285.full through http://cebp.aacrjournals.org. Accessed October 2010.
(2005 June 17). MTHFR Gene Variants and Birth Defects. CDC Birth Defects [On-line information] Available online at http://www.cdc.gov/ncbddd/bd/mthfr.htm through http://www.cdc.gov. Accessed October 2010.
(© 2010). MTHFR DNA Test. Kimball genetics [On-line information]. Available online at http://www.kimballgenetics.com/tests-mthfr.html through http://www.kimballgenetics.com. Accessed October 2010.