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Updated: Dec 25, 2025

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MTHFR genetic testing: Controversy and clinical implications.

Sarah Long, Jack Goldblatt

    Australian Family Physician
    |April 8, 2016
    PubMed
    Summary

    Genetic testing for methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms shows limited clinical utility. Current evidence suggests MTHFR testing is not recommended for general population screening due to inconclusive results.

    Area of Science:

    • Genetics
    • Clinical Medicine
    • Biochemistry

    Background:

    • Polymorphisms, such as MTHFR 677C>T and 1298A>C, are common gene variants.
    • These MTHFR polymorphisms are increasingly tested by various practitioners, despite conflicting data.
    • Weak associations exist between MTHFR polymorphisms and numerous health conditions.

    Purpose of the Study:

    • To address challenges in applying inconclusive genetic association study results to clinical practice.
    • To re-evaluate the role of polymorphism testing in diagnostic settings.
    • To clarify the clinical relevance of MTHFR gene variants.

    Main Methods:

    • Literature review of genetic association studies on MTHFR polymorphisms.
    • Analysis of clinical utility and diagnostic applicability of MTHFR testing.

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  • Evaluation of scientific evidence for MTHFR gene variants.

    • Main Results:

    • Inconclusive and conflicting data surround MTHFR polymorphisms.
    • Clinical relevance of MTHFR testing remains uncertain for many conditions.
    • Limited evidence supports widespread MTHFR gene testing.

    Conclusions:

    • Very limited clinical indications exist for MTHFR gene polymorphism testing (677C>T and 1298A>C).
    • MTHFR testing is not advisable as a non-specific screening tool for the asymptomatic general population.
    • Reconsideration of MTHFR polymorphism testing in clinical practice is warranted.