At a Glance

Why Become Tested?

To evaluate the cause of elevated homocysteine levels; sometimes to help determine your run a risk of thrombosis or premature cardiovascular affliction (CVD), though some expert guidelines practice non recommend information technology

When To Go 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

Sample Required?

A blood sample drawn from a vein

Test Grooming Needed?

None

What is being tested?

The methylenetetrahydrofolate reductase (MTHFR) gene contains the Deoxyribonucleic acid code to produce the MTHFR enzyme. This test detects ii of the well-nigh common mutations.

When there are mutations or variations in the MTHFR gene, it can pb to serious genetic disorders such equally homocystinuria, anencephaly, spina bifida, and others. The MTHFR enzyme is disquisitional for metabolizing one form of B vitamin, folate, into some other. It is likewise part of the process that converts homocysteine into methionine, an important building block for many proteins.

If someone has increased levels of homocysteine, that ways the body is not processing it properly. One crusade of that could exist a mutation in the MTHFR gene, causing homocystinuria. While at least seven unique MTHFR mutations have been constitute in people with homocystnuria, there are two relatively mutual Dna sequence variants, known every bit single nucleotide polymorphisms (SNPs), that are tested. The two MTHFR variants are called C677T and A1298C, and individuals can inherit one or both variants. These SNPs result in changes in the Dna (or mutations) that are associated with decreased MTHFR activity and increased homocysteine levels in the blood, which may increase the risk of premature cardiovascular disease (CVD), formation of inappropriate claret clots (thrombosis), and stroke.

Approximately 5-xiv% of the U.S. population is homozygous for C677T, meaning that they have two copies of it. There is some indigenous variability in the frequency, with the highest existence in those of Mediterranean beginnings and the lowest in those of African ancestry.

The C677T variant results in a less agile form of the MTHFR enzyme and reduced ability to process folate and homocysteine. When a person has ii copies of the MTHFR C677T factor mutation (homozygous) or one copy of MTHFR C677T and one copy of A1298C (compound heterozygous), decreased MTHFR enzyme activity slows downwardly the homocysteine-to-methionine conversion process and can lead to a buildup of homocysteine in the claret.

The increase in homocysteine is often balmy to moderate but will vary from person to person depending upon the amount of MTHFR enzyme activity. Even if a person has two copies of the MTHFR mutation, that person may not develop loftier homocysteine levels since acceptable folate intake can "cancel out" the event of the MTHFR mutation.

Results of some studies advise that loftier levels of homocysteine in the blood may contribute to gamble of CVD past dissentious claret vessel walls and promoting germination of plaque (atherosclerosis) and inappropriate blood clots. Still, a direct link betwixt homocysteine levels and cardiovascular disease or thrombotic run a risk has not been found. For more on this, encounter the article on Homocysteine.

Common Questions

How is it used?

The methylenetetrahydrofolate reductase (MTHFR) mutation test may be used to detect two relatively common mutations in the MTHFR cistron that are associated with elevated levels of homocysteine in the claret. It is non routinely ordered.

This test is sometimes ordered equally a follow-up to an elevated homocysteine test and may be occasionally ordered along with other cardiac risk tests if a person has a personal or family history of premature cardiovascular disease (CVD) or inappropriate blood clots (thrombosis). Yet, its utility for assessing risk of CVD has not been established and some expert guidelines do not recommend information technology for thrombosis screening.

Information technology may be ordered if a person has a close relative with known MTHFR genetic mutations, particularly if that person also has elevated homocysteine levels. MTHFR C677T and A1298C gene mutations are the most common and the ones that are typically tested. If someone has a unlike mutation in their family, then that specific mutation should be tested.

An MTHFR exam may sometimes be ordered along with other inherited clotting risk tests, such as Factor Five Leiden or prothrombin 20210 mutation tests to help evaluate a person's overall risk of developing inappropriate blood clots.

Although the MTHFR mutation test may be used to help determine the cause of elevated homocysteine, the value of measuring homocysteine levels is not clear. While bear witness from some studies suggests that elevated homocysteine levels contribute to the take a chance of CVD and/or thrombosis, a direct link has non been established. Routine testing for homocysteine levels as a cardiac risk marking is not recommended past the American Heart Association. The College of American Pathologists and the American College of Medical Genetics recommend confronting testing for the C677T variant, citing limited utility for patients with claret clots. Furthermore, use of homocysteine levels for the purpose of determining adventure of CVD, peripheral vascular illness, and stroke is in dubiety at this time given that several studies show no benefit or hazard reduction in people who were treated with folic acid and vitamin B supplements that lowered their homocysteine level.

When is it ordered?

The MTHFR mutation test may sometimes be ordered when a person has elevated homocysteine levels, especially when the person has a personal or family history of premature cardiovascular affliction or thrombosis. It may sometimes be ordered when a shut relative has MTHFR gene mutations, although it may non exist useful if that relative has normal homocysteine levels, and some laboratories and organizations recommend against using it for thrombophilia screening.

If a person is suspected to have high homocysteine levels, it is recommended to test for homocysteine level rather than MTHFR mutation. In a significant number of cases of homocysteinemia (increment in blood homocysteine level), the MTHFR mutation test is unnecessary.

What does the test outcome mean?

Results typically are reported as negative or positive and, if positive, the report will proper name the mutation(due south) present. Often, an interpretation of the results is too provided.

But a small per centum of cases of elevated homocysteine are due to an inherited cause. Of these, MTHFR C677T and A1298C mutations are amidst the most common.

If a person has two copies (homozygous) of MTHFR C677T, or has one copy of C677T and one of A1298C, then it is likely that elevated homocysteine levels are due to these inherited mutations, or that the mutations are contributing to them.

Two copies of A1298C are not typically associated with increased homocysteine levels.

If the MTHFR mutation test is negative, so the C677T and A1298C mutations were not detected and the tested person'south elevated homocysteine level is probable due to some other crusade. Other, more rareMTHFR genetic mutations will not be detected with typical testing.

Those with MTHFR mutations and other clotting gamble factors, such as Gene V Leiden or PT 20210 mutations, may be at an increased adventure of thrombosis. Research suggests that women with 2 C677T variants take double the risk of having a child with a neural tube defect, simply the risk is far below i%.

Is there anything else I should know?

People who accept elevated homocysteine levels may be at an increased risk of developing premature cardiovascular disease (CVD) and/or thrombosis, but many, including those with MTHFR mutations, will never develop CVD or thrombosis. A review of data published in 2012 determined that lifelong moderately elevated homocysteine levels had piddling to no effect on coronary heart affliction.

Too MTHFR mutations, there are other causes of elevated homocysteine levels, including deficiency of vitamins B6, B12, and/or folate; these vitamins are required for homocysteine metabolism. The MTHFR mutation may not be nowadays with these acquired, as opposed to inherited, causes of elevated homcysteine. Additionally, if a more rare mutation of MTHFR is causing elevated homocysteine levels, the C677T and A1298C tests will not detect those other mutations.

For MTHFR mutations, the C677T variant results in substitution of the amino acid alanine for valine. The A1298C variant results in an alanine substitution (versus a glutamine). The C677T valine commutation results in a less active form of the MTHFR enzyme.

A review of studies published in 2014 supported an clan between the MTHFR C677T allele and congenital heart disease in Asian populations and the A1298C allele and CHD in the pediatric Caucasian population.

The MTHFR enzyme is involved in folate metabolism. Because of this, those who take MTHFR mutations and take drugs that bear upon folate metabolism, such as methotrexate, may exist more than likely to experience toxicity. An MTHFR mutation examination may be performed for a person who is prescribed methotrexate in order to adjust dosages and reduce risk of toxicity.

Who performs MTHFR testing?

It is not offered in every laboratory. In near cases, your blood will be sent to a reference laboratory for testing.

Can my MTHFR genes change?

No, y'all inherit a copy of the cistron from each of your parents and they will not change over time.

If I have the same MTHFR gene mutations as a relative, why is my homocysteine level significantly different?

Even when ii people take the same MTHFR mutations, the results and their risks are oft different. Many things can bear upon homocysteine levels, including MTHFR enzyme action, folate or other B vitamin levels, and a person's health condition.

View Sources

Sources Used in Current Review

5,ten-Methylenetetrahydrofolate Reductase C677T and A1298C Mutations, Blood. Mayo Medical Laboratories. Available online at https://www.mayomedicallaboratories.com/exam-catalog/Clinical+and+Interpretive/61367. Accessed on 8/21/18.

(September 27, 2018) A Genetic Test You Don't Demand. Cleveland Clinic. Bachelor online at https://health.clevelandclinic.org/a-genetic-test-you-dont-need. Accessed on 8/21/18.

Homocysteine. University of Rochester Medical Center. Bachelor online at https://world wide web.urmc.rochester.edu/encyclopedia/content.aspx?ContentTypeID=167&ContentID=homocysteine. Accessed on 8/21/18.

(Dec 4, 2014) Association Betwixt MTHFR Polymorphisms and Congenital Heart Illness: A Meta-analysis based on 9,329 cases and 15,076 controls.Scientific Reports. Available online at https://world wide web.ncbi.nlm.nih.gov/pmc/manufactures/PMC4255188. Accessed on 8/22/xviii.

(February 21, 2012) Homocysteine and Coronary Centre Illness: Meta-analysis of MTHFR Case-Control Studies, Fugitive Publication Bias. PLOS Medicine. Available online at https://journals.plos.org/plosmedicine/article?id=ten.1371/journal.pmed.1001177. Accessed on 8/22/18.

MTHFR Gene Variant. Genetic and Rare Diseases Data Centre, National Eye for Advancing Translational Sciences, National Institutes of Health. Available online at https://rarediseases.info.nih.gov/diseases/10953/mthfr-cistron-variant. Accessed on 8/22/18.

Sources Used in Previous Reviews

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. Accessed October 2010.

(Reviewed 2008 Jan). MTHFR. Genetics Home Reference [On-line data]. Available online at http://ghr.nlm.nih.gov/cistron/MTHFR. Accessed Oct 2010.

Fong, C. (Revised 2010 Feb). Amino Acid and Organic Acid Metabolism Disorders. Merck Manual for Healthcare Professionals [On-line information]. Available online at http://world wide web.merck.com/mmpe/sec19/ch296/ch296c.html?qt=MTHFR&alt=sh. 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. Accessed Oct 2010.

(© 1995-2010). MayoClinic Mayo Medical Laboratories. Unit of measurement Code 91457: Methylenetetrahydrofolate Reductase (MTHFR) 2 Mutations [On-line information]. Available online at http://www.mayomedicallaboratories.com/test-catalog/Overview/91457. Accessed October 2010.

(© 2006-2010). Methylenetetrahydrofolate Reductase (MTHFR) 2 Mutations: 0055655. ARUP'southward Laboratory Examination Directory [On-line information]. Bachelor online at http://www.aruplab.com/guides/ug/tests/0055655.jsp. Accessed October 2010.

Varga, E. et. al. (2005 May 17). Homocysteine and MTHFR Mutations, Relation to Thrombosis and Coronary Artery Disease. Apportionment. 2005;111:e289-e293 [On-line information]. Available online at http://circ.ahajournals.org/cgi/content/full/111/19/e289. Accessed October 2010.

Curtin, 1000. et. al. (2004 February). MTHFR C677T and A1298C Polymorphisms. Cancer Epidemiology, Biomarkers & Prevention. Feb 1, 2004 13; 285 [On-line data]. Bachelor online at http://cebp.aacrjournals.org/content/13/2/285.total. Accessed October 2010.

(2005 June 17). MTHFR Factor Variants and Nativity Defects. CDC Nascency Defects [On-line data] Available online at http://www.cdc.gov/ncbddd/bd/mthfr.htm. Accessed October 2010.

(© 2010). MTHFR DNA Test. Kimball genetics [On-line information]. Bachelor online at http://www.kimballgenetics.com/tests-mthfr.html. Accessed October 2010.

(Reviewed 2011 July). MTHFR. Genetics Home Reference. Bachelor online at http://ghr.nlm.nih.gov/gene/MTHFR. Accessed February 2014.

(© 1995-2014). 5,10-Methylenetetrahydrofolate Reductase C677T, Mutation, Claret. Mayo Medical Laboratories. Available online at http://world wide web.mayomedicallaboratories.com/test-catalog/Clinical+and+Interpretive/81648. Accessed Feb 2014.

(© 2014). Methylenetetrahydrofolate Reductase (MTHFR) 2 Mutations 0055655. ARUP Laboratories Laboratory Test Directory. Available online at http://ltd.aruplab.com/Tests/Pub/0055655. Accessed February 2014.

Wang W. et al. (2013 March 11). MTHFR C677T Polymorphism and Risk of Congenital Eye Defects: Evidence from 29 Case-Control and TDT Studies. PLOS One. DOI: x.1371/journal.pone.0058041. Available online at http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0058041. Accessed February 2014.

Hickey, Due south. et al. (3 January 2013). ACMG Practice Guideline: lack of evidence forMTHFR polymorphism testing. Genetics in Medicine. doi:10.1038/gim.2012. Available online at http://world wide web.nature.com/gim/journal/v15/n2/total/gim2012165a.html. Accessed February 2014.

Cohen D.A., et al. (29 Nov 2013). Laboratory informatics based evaluation of methylene tetrahydrofolate reductase C677T genetic examination overutilization. Journal of Pathology Informatics. doi: 10.4103/2153-3539.122389. Available online at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3869957/. Accessed February 2014.

Mandava, P. et al. (Updated 2013 June xx). Homocystinuria/Homocysteinemia. Medscape. Available online at http://emedicine.medscape.com/article/1952251-overview#a30. Accessed Feb 2014.

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