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The genetic code hidden in MTHFR: How powerful are these genetic variants?
In the scientific community, the gene methyltetrahydrofolate reductase (MTHFR) is gradually attracting people's attention. This gene is located at the p36.3 position on the first human chromosome. The encoded enzyme is a rate-limiting enzyme in the methyl cycle, responsible for converting 5,10-methyltetrahydrofolate into 5-methyltetrahydrofolate. This is then used to convert homocysteine into methionine. In nature, MTHFR mutations are quite common in healthy people, but are these genetic mutations really as powerful as rumored?
Natural variation in this gene is common in otherwise healthy people.
The impact of genetic variation
Certain variations in the MTHFR gene are associated with susceptibility to a variety of diseases, including vaso-occlusive disease, neural tube defects, Alzheimer's disease and other forms of dementia, colon cancer, and acute leukemia. Although early small studies reported such associations, subsequent large-scale studies have not replicated these results.
Biochemical functions of MTHFR
MTHFR irreversibly reduces 5,10-methyltetrahydrofolate to 5-methyltetrahydrofolate in the rate-limiting step of the methyl cycle. This reaction process is essential for making thymidylate, and 5-methyltetrahydrofolate also converts homocysteine, a toxic amino acid, into methionine. The structure of MTHFR consists of an N-terminal catalytic domain and a C-terminal regulatory domain, with at least two promoters and two isoforms (70 kDa and 77 kDa).
Specific types of genetic mutations
C677T SNP
Among the two possibilities of C (cytosine) or T (thymine) at position 677 of the MTHFR gene, C is the reference allele. The 677T allele encodes a heat-sensitive variant with reduced activity. The frequency of this variant in different ethnic groups ranges from 10% to 35%. Individuals with type 677TT have lower MTHFR activity than type 677CC or 677CT and are more likely to develop mild homocystinemia.
Individuals with two copies of 677C have the most common genotype.
A1298C SNP
At position 1298 of MTHFR, there are two possibilities, A or C. 1298A is the most common type, while 1298C is relatively rare. Research shows that the 1298C mutation does not seem to significantly affect the function of MTHFR, but it has a certain impact on the production of neurotransmitters.
Detection and clinical utility
Although genetic testing is gradually gaining attention, the American College of Medical Genetics (ACMG) has issued official guidance on the clinical utility of C677T and A1298C mutations, deeming such testing unnecessary because there is currently no clear evidence of causality.
There is growing evidence that MTHFR polymorphism testing has minimal clinical utility.
Controversy about MTHFR
As genetic testing becomes more popular, MTHFR variants have become the focus of some alternative medicine therapies. However, publicity about MTHFR mutations is often accompanied by a disregard for scientific evidence, and many so-called treatments lack substantial support for health effects.
Conclusion
Research on MTHFR is revealing the multiple roles it may play in health and disease. As our understanding of this gene continues to deepen, should we re-examine the power and meaning behind these genetic codes?
