Genomics in general practice

MTHFR gene testing

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Last revised: 30 Nov 2018

Practice point

There is no substantial evidence to support the use of MTHFR gene testing in routine clinical practice.

Knowledge of MTHFR gene status is unlikely to change patient management.^1–3

What do I need to know?

The MTHFR gene is involved in processing amino acids, specifically in relation to folate metabolism.

The MTHFR gene test identifies two gene variants associated with increased levels of homocysteine in the blood (C677T and A1298C). These variants are common in the general population.³

MTHFR gene testing is promoted by some complementary and alternative practitioners to investigate infertility, recurrent pregnancy loss and risk for particular diseases. However:^1–3

There is no significant evidence of a causal link between MTHFR gene variants and particular diseases.
MTHFR status does not alter the recommendation that women who are planning a pregnancy or those in the first trimester of pregnancy take folic acid supplements to reduce the risk of neural tube defects.

Patients can obtain MTHFR gene testing through private providers at their own expense.

There is no indication to refer the patient to genetics services. Given the lack of clinical utility, some genetics service providers are no longer accepting patient referrals for consultations in relation to MTHFR.³

How can I manage MTHFR gene testing in general practice?

Advising patients who are considering MTHFR gene testing

The following points may be useful to raise in a discussion with patients who are interested in ordering a MTHFR gene test:

MTHFR gene testing is not recommended when:
- many people have one or both MTHFR gene variants (C677T and/or A1298C)³
- there is a lack of strong scientific evidence to show that having one or both MTHFR gene variants causes particular health problems^1,3,4
- there are no evidence-based treatments that will improve the health of a patient with one or both of the MTHFR gene variants.³

There is an association between the presence of MTHFR gene variants and increased homocysteine levels; however
- while high homocysteine was once thought to increase risk of blood clots (thrombophilia), cardiovascular disease (CVD) and recurrent pregnancy loss, recent studies have found that this is not the case^1,4
- many other factors also increase homocysteine (ie diet, lifestyle, other gene variants). A person can reduce their risk of disease by following a healthy, balanced diet and avoiding well-known risk factors such as smoking and being overweight
- having a biochemical test for homocysteine levels may provide more useful information. This is less expensive than having a MTHFR gene test, which in most cases is not covered under the Medicare Benefits Schedule (MBS).

Managing patients who have had MTHFR gene testing

The following points may be useful in a discussion with a patient who has had a MTHFR gene test and is concerned about the results:

The presence of one or both MTHFR gene variants (C677T and/or A1298C) is not associated with particular health problems
- Individuals who have the MTHFR gene variant(s) might have increased homocysteine levels. While this was once thought to be associated with particular health problems (ie thrombophilia, CVD, recurrent pregnancy loss), recent studies have found that this is not the case.^1,4 Many other factors also increase homocysteine (ie diet, lifestyle, other gene variants). A person can reduce their risk of disease by following a healthy, balanced diet and avoiding well-known risk factors such as smoking and overweight.
- Women who have MTHFR gene variant(s) may have a slightly increased risk of having a baby with neural tube defects (eg spina bifida). However, taking folic acid supplements before and during pregnancy decreases the risk, just as it does in women who do not have MTHFR gene variant(s).
Genetic services are unlikely to accept referrals for consultations about the results of MTHFR gene testing because the presence of MTHFR gene variants is unlikely to significantly affect a patient’s health.

Resources for general practitioners

The Royal Australian College of General Practitioners, Position statement on responding to patient requests for tests not considered clinically appropriate
The Royal College of Pathologists of Australasia, Position statement: MTHFR genetic tests
The Royal Australian College of General Practitioners, Chapter 15, Screening tests of unproven benefit – Guidelines for preventive activities in general practice

Resources for patients

Centre for Genetics Education, Fact sheet 64: MTHFR gene test for patients
The Royal Australian College of General Practitioners, Appropriate diagnostic testing: Patient information

References

Hickie SE, Curry CJ, Toriello HV. ACMG Practice Guideline: Lack of evidence for MTHFR polymorphism testing. Genet Med 2013;15(2):153–56 [Accessed 22 December 2017].
Human Genetics Society of Australasia and Choosing Wisely Australia. 5 things clinicians and consumers should question. Sydney: NPS MedicineWise, 2016 [Accessed 22 December 2017].
Long S, Goldblatt J. MTHFR genetic testing: Controversy and clinical implications. Aust Fam Physician 2016;45(4):237–40 [Accessed 7 July 2017].
Levin BL, Varga E. MTHFR: Addressing genetic counseling dilemmas using evidence-based literature. J Genet Couns 2016;25(5):901–11. [Accessed 7 July 2017].

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