MTHFRE GENE

 MTHFRE GENE

The MTHFR gene codes for a key 

enzyme in folate metabolism. 

A large number of studies have

The associated the presence of 

common variants in the C677T and 

A1298C populations

 with a decreased folate metabolic capacity that could be related to several clinical conditions.

The MTHFR gene encodes for the enzyme methylene tetrahydrofolate reductase which plays

 a key role in folate and homocysteine metabolism by catalyzing the conversion of dietary

 ingested folate (vitamin B9) into the main circulating form of folate which is used in the 

conversion pathway of homocysteine to methionine. Methionine is an essential amino acid,

 not only for the constitution of the body's proteins, but also for DNA methylation and regulation 

of gene expression. In this sense, changes in the MTHFR gene sequence can lead to deficiency

 of this enzyme, and with this, to alterations in the folate conversion cycle and in the generation

 of methionine from homocysteine, which can lead to low levels of folate in blood and elevated 

levels of homocysteine in blood and urine (homocystinuria).

Variants in the MTHFR gene C677T and A1298C are two of the most common polymorphisms

 in the general population. Approximately 60-70% of individuals will have at least one of these 

variants, 8.5% will be homozygous (two copies) for one of them, and 2.25% will be compound 

heterozygous carriers (one copy of each variant). Both variants have been associated with

 reduced MTHFR enzyme activity, and reduced efficiency in folic acid processing. The C677T

 change decreases the affinity of MTHFR and its cofactor, which favors thermolability and 

decreasesn enzyme activity, whereas A12958C directly decreases enzyme activity. Hence,

 these variants have been associated with a variety of conditions, including various cancers, 

coronary artery disease, altered plasma lipid levels and neural tube closure defects, as well as

 thrombophilias, fertilityr Problems and complications during pregnancy.

However, despite the vital role of folate and MTHFR in its metabolism, scientific findings remain

 inconsistent and without statistically significant evidence that these polymorphisms have an

 impact on routine clinical practice. In this context, the American College of Medical Genetics

 and Genomics does not recommend the determination of the two common polymorphisms

 on a routine basis, and likewise, the American Academy of Nutrition and Dietetics does not 

recommend dietary interventions. This is because both variants have high frequencies in

 the general population, and there are no clinically meaningful interventions that can be

 offered to carriers, so their identification is not currently useful.

In addition to diet and other pathophysiological conditions (hypothyroidism, renal 

insufficiency

, arterial hypertension, diabetes mellitus, smoking or physical inactivity among 

others), the genetic

 component can affect homocysteine levels. The two widely studied common

 variants, C677T and

 A1298C, have been linked to a decrease in the activity of the MTHFR gene, which

 codes for the

 methylenetetrahydrofolate reductase enzyme involved in the folate cycle, which

 could affect 

intracellular folate distribution and increase homocysteine levels moderately.

 Both variants are

 prevalent in the population as a whole, both single copy or two copies of 

either variant, and 

one copy of each of the two variants.

Number of observed variants

13.5 million variants

Number of variants analyzed 

in the study

2 variants

Bibliography

MTHFR genetic testing: Controversy and clinical implications.

 Australian Journal for General Practitioners 2016; 45(4):237-240.

Wan L et al. Methylenetetrahydrofolate reductase and psychiatric 

diseases. Transl Psychiatry 2018; 8, 242.

Leclerc D et al. Molecular Biology of Methylenetetrahydrofolate

 Reductase (MTHFR) and Overview of Mutations/Polymorphisms. 

Madame Curie Bioscience Database [May 2022].

Liu F et al. 5,10-methylenetetrahydrofolate reductase C677T gene 

polymorphism and peripheral arterial disease: A meta-analysis. 

Vascular. 2020:1708538120982698.

Osadnik T et al. Genetic and environmental factors associated with 

homocysteine concentrations in a population of healthy young adults. 

Analysis of the MAGNETIC study. Nutr Metab Cardiovasc Dis. 2020;30(6):939-947.

TELLMEGEN.COM was used to create this report for science to use on my DNA

that is above. Hope this can help others.