Panel: Genetic predisposition to folate cycle disorders

Why it matters

Folates are essential for cell division, DNA synthesis and many metabolic processes. Their proper absorption and conversion largely depend on enzyme activity, which can be influenced by genetic variations. In some people, these variations may affect folate and homocysteine metabolism.

Genetic testing helps identify such inherited characteristics. The physician interprets the results alongside homocysteine, folate and vitamin B12 levels to personalise the form and dosage of folates and B vitamins when required and determine whether further monitoring is needed.

Folates are essential for cell division and the development of the nervous system, so genetic testing can complement a comprehensive assessment of a woman’s folate status.

How the body uses folates

Once absorbed, folates undergo a series of biochemical transformations in the body. Their active forms are required for one-carbon transfer reactions, methylation processes and the conversion of homocysteine into methionine. Each stage relies on specific enzymes, cofactors and cellular transport mechanisms.

The MTHFR, MTR and MTRR genes are involved in successive stages of this metabolic pathway. SLC19A1 encodes a transport protein that helps folates enter cells.

Analysis of these four genes provides insight into several stages of folate metabolism and complements laboratory findings with information about inherited characteristics of these processes.

Folate cycle genetics and its role in health

Folate metabolism includes the processes that allow the body to absorb and use folates while also regulating homocysteine levels. Folate cycle genes influence how this system functions, which means folate metabolism can vary from person to person. Folate cycle genetic testing helps identify inherited variants in the MTHFR, MTR, MTRR and SLC19A1 genes. However, a genetic test alone cannot determine whether a folate cycle disorder is present. The physician also considers homocysteine, folate and vitamin B12 levels, along with other relevant blood markers.

A comprehensive folate metabolism test provides a clearer picture of folate metabolism and helps personalise the form and dosage of folates and B vitamins, as well as determine whether further monitoring is needed.

Genetic characteristics of folate metabolism

Characteristics of homocysteine conversion

Inherited characteristics of methylation processes

Genetic factors associated with homocysteine levels

Characteristics of folate transport into cells

Additional data for personalised folate and B vitamin supplementation

Elevated homocysteine levels

Folate and vitamin B12 deficiency

Prevention of early atherosclerosis

Cardiovascular risk assessment

Arterial hypertension

Ischaemic heart disease

Cerebrovascular disorders

Thrombotic complications

Personalisation of folate and B vitamin supplementation

Conditions following bariatric surgery

Anaemia of unknown origin

Prevention of foetal neural tube defects

Female and male infertility

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Programme components

The check-up includes 4 genes, each associated with a specific stage of folate metabolism. Some are involved in the formation and utilisation of active folate forms, while others contribute to homocysteine and methionine metabolism or facilitate folate transport into cells. Together, these findings provide a more detailed picture of the inherited characteristics of this biochemical system.

MTHFR gene

For folates to participate effectively in metabolic processes, the body needs to convert them into biologically active forms. One of the key reactions is carried out by the enzyme methylenetetrahydrofolate reductase, which is encoded by the MTHFR gene.
The panel examines the C677T (rs1801133) and A1298C (rs1801131) polymorphisms. Certain variants may alter enzyme activity and influence individual characteristics of folate and homocysteine metabolism.

MTR gene

At one stage of the folate cycle, homocysteine is converted into methionine. This reaction is carried out by methionine synthase, an enzyme encoded by the MTR gene. Vitamin B12 is also required for the enzyme to function normally.
MTR analysis complements the genetic assessment of the mechanisms involved in homocysteine remethylation and methionine formation.

MTRR gene

Methionine synthase needs to have its activity continuously restored. This process is supported by another enzyme encoded by the MTRR gene.
MTRR therefore represents a separate component of the same biochemical pathway. Genetic variants may influence how efficiently methionine synthase activity is restored and, in turn, affect homocysteine and folate metabolism.

SLC19A1 gene

Before folates can take part in cellular reactions, they first need to enter the cell. This process involves the RFC1 transport protein, which is encoded by the SLC19A1 gene.
Analysis of the c.45537880T>C variant provides additional information about inherited characteristics of cellular folate transport and complements the overall assessment of folate metabolism.