How Genes Influence Your Homocysteine Levels

What Is Homocysteine?

Homocysteine is a non-protein amino acid generated in the body during the metabolism of methionine, an essential amino acid acquired from the diet.

Normal homocysteine levels are maintained by two metabolic pathways: remethylation and transsulfuration.

These processes, facilitated by various vitamins (B6, B9, B12) and enzymes, help regulate homocysteine levels in the body.

What is Hyperhomocysteinemia?

Hyperhomocysteinemia is a medical condition characterized by high levels of homocysteine in the blood.

High homocysteine levels have been associated with a range of health problems, including cardiovascular disease, stroke, and neurological conditions.

It can also lead to complications during pregnancy, such as pre-eclampsia and neural tube defects in the newborn.

Genetics And Homocysteine Levels

Several genes are involved in the metabolism of homocysteine, and variations in these genes can influence homocysteine levels in the body. Here, we explore a few key genes involved in homocysteine metabolism.

MTHFR Gene

One of the primary genes implicated in homocysteine metabolism is the MTHFR gene, which encodes for the enzyme methylenetetrahydrofolate reductase.

This enzyme is crucial for the conversion of homocysteine to methionine.

Certain variants in this gene, like the C677T and A1298C, are known to reduce the efficiency of this enzyme, leading to increased homocysteine levels in the blood.

Check your AncestryDNA, 23andMe raw data for the MTHFR gene variants

CBS Gene

The CBS gene, coding for the enzyme cystathionine-beta-synthase, is also involved in the regulation of homocysteine levels.

This enzyme helps convert homocysteine to cystathionine in the transsulfuration pathway. Mutations in the CBS gene can disrupt this process, causing homocysteine to accumulate.

Check your AncestryDNA, 23andMe raw data for the CBS gene variants

MTR and MTRR Genes

MTR (methionine synthase) and MTRR (methionine synthase reductase) genes are also important in the metabolism of homocysteine.

MTR helps convert homocysteine to methionine, and MTRR helps keep MTR in its active form.

Variants in these genes can influence the effectiveness of these conversions, thereby affecting homocysteine levels.

Check your AncestryDNA, 23andMe raw data for the MTR & MTRR gene variants

Others

Other genes like MMACHC (methylmalonic aciduria and homocystinuria type C protein) and MTHFD1 (methylenetetrahydrofolate dehydrogenase 1) are also implicated in the metabolism of homocysteine.

Check your AncestryDNA, 23andMe raw data for the MMACHC gene variants

Section Summary

Several genes are involved in maintaining optimal homocysteine levels in the body, and genetic variants in these genes can potentially lead to higher homocysteine levels, a condition known as hyperhomocysteinemia. Testing for these genetic variations can help identify individuals at risk for hyperhomocysteinemia and provide personalized dietary recommendations for maintaining healthy homocysteine levels.

Non-Genetic Factors Influencing Homocysteine Levels

Apart from genetics, various lifestyle, and environmental factors can influence homocysteine levels.

These include nutritional deficiencies (especially in vitamins B6, B9, and B12), age, smoking, excessive alcohol consumption, lack of physical activity, and certain medications.

Symptoms Of Hyperhomocysteinemia

Often, hyperhomocysteinemia doesn’t present with visible symptoms until it leads to serious health complications.

However, depending on the underlying cause and severity, symptoms may include fatigue, dizziness, chest pain, difficulty concentrating, and numbness or tingling in hands and feet.

Maintaining optimal homocysteine levels

Maintaining optimal homocysteine levels involves a combination of dietary modifications and lifestyle changes. Consuming a balanced diet rich in vitamins B6, B9, and B12, which aid in the metabolism of homocysteine, is crucial. Regular exercise, maintaining a healthy weight, quitting smoking, and reducing alcohol intake can also help manage homocysteine levels.

Testing For Homocysteine Levels

Homocysteine levels are typically checked using a blood test. These tests can help identify if your homocysteine levels are high, potentially indicating a risk of developing certain health conditions or the presence of a genetic variation affecting homocysteine metabolism.

Summary

Homocysteine is a key player in several metabolic processes in the body. Keeping its levels within the normal range is essential for maintaining overall health. Understanding both the genetic and non-genetic factors that influence homocysteine levels can help manage the risk associated with hyperhomocysteinemia.

References

• Selhub, J. (1999). Homocysteine metabolism. Annual review of nutrition, 19, 217-246.
• Refsum, H., Ueland, P. M., Nygård, O., & Vollset, S. E. (1998). Homocysteine and cardiovascular disease. Annual review of medicine, 49, 31-62.
• Schwahn, B., Rozen, R. (2001). Polymorphisms in the methylenetetrahydrofolate reductase gene: clinical consequences. American Journal of Pharmacogenomics, 1(3), 189-201.
• Poddar, R., Sivasubramanian, N., DiBello, P. M., Robinson, K., & Jacobsen, D. W. (2001). Homocysteine induces expression and secretion of monocyte chemoattractant protein-1 and interleukin-8 in human aortic endothelial cells: implications for vascular disease. Circulation, 103(22), 2717-2723.
• Brustolin, S., Giugliani, R., & Félix, T. M. (2010). Genetics of homocysteine metabolism and associated disorders. Brazilian Journal of Medical and Biological Research, 43(1), 1-7.