Unraveling the Mystery of MTHFR Thermolabile Polymorphism: A Guide to Understanding, Diagnosing, and Genetic Testing

Short answer: The MTHFR thermolabile polymorphism, identified as rs1801133 (G>A) and historically called C677T, is a common variant in the MTHFR gene that lowers the activity of an enzyme used in folate metabolism. Having it does not mean you will develop a health problem, and it usually does not change medical care or standard folic acid advice. The American College of Medical Genetics and Genomics (ACMG) says testing for this variant has minimal clinical use and should not be ordered as part of a routine evaluation for blood clotting disorders.

What Do Medical Guidelines Say About MTHFR Testing?

In 2013 the American College of Medical Genetics and Genomics (ACMG) reviewed the evidence on MTHFR polymorphism testing. It reported that recent studies disproved an association between high homocysteine and coronary heart disease, and between MTHFR polymorphism status and venous thromboembolism. It concluded that testing has minimal clinical use and should not be ordered as part of a routine evaluation for thrombophilia. If you are worried about homocysteine, a blood test can measure it directly. Talk with your doctor before you make decisions about diet, supplements or medicines based on an MTHFR result.

Understanding MTHFR Thermolabile Polymorphism

The MTHFR thermolabile polymorphism is a common variant in the methylenetetrahydrofolate reductase (MTHFR) gene, identified as rs1801133 (G>A) and historically called C677T. The MTHFR gene helps the body use folate, an essential nutrient involved in DNA synthesis and repair. The variant lowers the activity of the MTHFR enzyme, which in some people, especially with low folate, can lead to higher homocysteine levels. A second common variant, rs1801131 (T>G), is historically called A1298C.

Several studies have explored the prevalence and distribution of MTHFR C677T polymorphism across different populations. For instance, a study examining the relationship between MTHFR C677T polymorphism prevalence and ultraviolet radiation in Eurasia found an inverse U-shape association, suggesting a possible interaction between genetic and environmental factors (source). Another study comparing the genetic distribution of MTHFR Thermolabile Polymorphism between the Mongolian and Han populations in China revealed significant differences, with a higher mutant frequency in the Han population (source).

Diagnosing MTHFR Thermolabile Polymorphism

Genetic testing can identify the rs1801133 (G>A) variant, historically called C677T, from a blood sample, and show whether a person carries one or two copies of it. Having the variant does not guarantee any health problem, because other genetic and environmental factors also contribute to risk.

What Testing Means in Practice

Genetic testing for MTHFR Thermolabile Polymorphism can be helpful in several ways:

• Risk assessment: The common variant alone does not usually change medical care. Most people who carry it have normal homocysteine, and testing is not part of a routine evaluation for heart disease or blood clotting disorders (ACMG, 2013).
• Folic acid advice: Standard folic acid advice is the same whether or not you have the variant. The CDC recommends 400 micrograms of folic acid every day for people who could become pregnant. Talk with your doctor before starting high dose supplements.
• Family planning: A result does not usually change standard pregnancy advice. If you are planning a pregnancy, or neural tube defects or clotting disorders run in your family, talk with your doctor or a genetic counselor.

Current Research on MTHFR Thermolabile Polymorphism

Recent studies continue to investigate the impact of MTHFR C677T polymorphism on health outcomes and its interaction with environmental factors. For example, a study examining the interplay between exposure to polycyclic aromatic hydrocarbons (PAHs) and MTHFR C677T polymorphism on cardiovascular risk biomarkers in Mexican women found a significant association between PAH exposure and increased cardiovascular risk, particularly in women carrying the MTHFR C677T polymorphism (source). Another study suggested that the APOE rs7412 T/T genotype, rather than MTHFR rs1801133 genotype, may be a risk factor for essential hypertension among the Hakka population in Southern China (source).

In conclusion, the common MTHFR variant rs1801133 (G>A), historically called C677T, usually does not change medical care or standard folic acid advice. Ongoing research continues to study how it interacts with genetic and environmental factors.

Related Articles

• MTHFR Gene: Variants, Testing and What Your DNA Can Tell You: our full guide to the MTHFR gene.
• Decoding Elevated Homocysteine Levels: how homocysteine is measured and what raises it.
• Homocystinuria due to MTHFR Deficiency: the rare, severe condition, which is different from the common variant.

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Whole genome sequencing reads 100% of your DNA, which includes the MTHFR gene and more than 30,000 others. Sequencing's Kit Bundles include a Whole Genome Sequencing kit and Next Gen Disease Screening, which analyzes your genome for more than 15,000 conditions. Medical guidelines advise against relying on the common MTHFR variant alone, so bring your results to a doctor or genetic counselor.

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Frequently Asked Questions About MTHFR Thermolabile Polymorphism (C677T)

What is the MTHFR thermolabile polymorphism?

It is a genetic variation in the MTHFR gene, commonly called C677T. The change reduces the activity of the MTHFR enzyme, which helps the body use folate, a nutrient involved in DNA synthesis and repair.

Does having the C677T variant mean I will get sick?

No. Having the variant does not guarantee a health problem, because other genetic and environmental factors also affect risk. In some people it can lead to higher homocysteine levels.

Should I get tested for the MTHFR variant?

Medical guidelines say not as a routine test. ACMG advises that MTHFR polymorphism testing has minimal clinical use and should not be ordered as part of a routine evaluation for thrombophilia. If you are concerned about homocysteine, ask your doctor about a blood test that measures it.

How common is the variant?

How common it is differs between populations. Studies have found differences between the Mongolian and Han populations in China, and have looked at links with ultraviolet radiation across Eurasia.

Does Sequencing test for the MTHFR variant?

Sequencing's whole genome sequencing reads 100% of your DNA, which includes the MTHFR gene, so the variant appears in your data. Because guidelines advise against using it on its own to guide care, review any result with a doctor or genetic counselor.

References

1. Hickey SE, Curry CJ, Toriello HV. ACMG practice guideline: lack of evidence for MTHFR polymorphism testing. Genet Med. 2013;15(2):153-156. doi:10.1038/gim.2012.165
2. MedlinePlus Genetics. MTHFR gene. medlineplus.gov/genetics/gene/mthfr
3. MedlinePlus. Homocysteine test. medlineplus.gov/lab-tests/homocysteine-test

This article is for education and is not a substitute for professional medical advice, diagnosis, or treatment. Talk to a qualified healthcare provider about your own health.