BHMT: Genetic Variants that Impact Methylation

The methylation cycle is an essential pathway for producing methyl groups, which are used by the body in a billion reactions. One role of methylation is to metabolize homocysteine, which is an amino acid that is a risk factor for heart disease.

This article goes over the role of BHMT in the methylation cycle and explains how genetic variants in the gene can impact your need for certain nutrients.

What does the BHMT enzyme do?

The BHMT (betaine homocysteine S-methyltransferase) enzyme is mainly found in the liver. It helps cells to convert homocysteine into methionine.

Let’s break this down:

  • Homocysteine production happens in the methylation cycle and is part of how the body produces methyl groups. High homocysteine levels have links to heart disease and hearing loss.
  • Methionine is an amino acid used by the body in a million ways. It is abundant in food sources, and the body can also make it in a couple of ways, including the reaction involving BHMT.
  • Betaine is also known as trimethylglycine (TMG).

The reaction catalyzed by BHMT:

Trimethylglycine (methyl donor) + homocysteine (hydrogen donor) →
dimethylglycine (hydrogen receiver) + methionine (methyl receiver)

To sum up: In the liver, the BHMT enzyme methylates homocysteine in order to produce the needed methionine. This not only helps to keep homocysteine at an appropriate level but also produces a vital amino acid (methionine).[ref]

Understanding the role of BHMT in the methylation cycle

As I mentioned above, the BHMT enzyme involves one way that the body converts homocysteine back to methionine. Another way that cells do this is by using the enzyme methionine synthase.

Within the methylation cycle, MTHFR gene variants limit methyl groups produced in the folate cycle. This is linked to higher homocysteine levels in some people due to not enough methionine synthase being available to convert homocysteine back to methionine.

The BHMT enzyme can step into that gap — but not in people with genetic variants that decrease the enzyme function.

Impacts of decreases in the methylation cycle:

Neural tube defects are a type of birth defect that can occur when there are not enough methyl groups available during pregnancy. This is why folic acid is added to prenatal vitamins and some processed foods in many countries.

Cancer rates, such as for breast cancer, increase with low folate – either through genetic variants impacting the methylation cycle or through poor diet. Consuming enough folate-rich foods matters a lot. Many of the genetic variants only have links to an increase in the risk of cancer for people who don’t eat enough folate and/or choline.[ref][ref]

While the body has a couple of ways of metabolizing homocysteine, BHMT is important here. In the liver, BHMT is responsible for about half of homocysteine metabolism.[ref]

High homocysteine is a marker associated with elevated heart disease risk. A number of genetic variants in the methylation cycle genes have links to higher homocysteine levels as well as heart disease.[ref] The increase in risk can be reduced through the right dietary intake of folate and other B-vitamins.[ref]


Genetic variants: BHMT

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The following SNP (rs3733890 ) is the best research genetic variant in BHMT with many studies showing that it has an impact on enzyme function:

Check your genetic data for rs3733890 R239Q G716A (23andMe v4, v5; AncestryDNA):

  • A/A: reduced BHMT[ref][ref] reduced conversion of choline to betaine[ref] increased risk of early-onset heart disease with poor diet[ref]
  • A/G: reduced BHMT, reduced conversion of choline to betaine, increased risk of early-onset heart disease with poor diet
  • G/G: typical

Members: Your genotype for rs3733890 is .

These variants may have a more minor impact on BHMT function:

Check your genetic data for rs651852 (23andMe v4 only):

  • C/C: increased risk of cleft lip, an indicator of low methyl groups[ref]
  • C/T: typical
  • T/T: typical

Members: Your genotype for rs651852 is .

Check your genetic data for rs567754 (23andMe v4, v5; AncestryDNA):

  • C/C: typical
  • C/T: decreased risk of ER-negative breast cancer
  • T/T: decreased risk of ER-negative breast cancer.[ref]

Members: Your genotype for rs567754 is .


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Related Articles and Topics:

Folate & MTHFR
The MTHFR gene codes for a key enzyme in the folate cycle. MTHFR variants can decrease the conversion to methyl folate.

CBS variants and low sulfur
This article digs into the high-quality research on the common CBS genetic variants to determine if there is any evidence suggesting everyone should be on a low-sulfur diet. Read through the research and check your genetic data.

COMT – A gene that affects your neurotransmitter levels
Having trouble with supplements containing methyl groups? Wondering why your neurotransmitters are out of balance? It could be due to your COMT genetic variants. This important enzyme is tasked with breaking down neurotransmitters, such as dopamine.


About the Author:
Debbie Moon is the founder of Genetic Lifehacks. Fascinated by the connections between genes, diet, and health, her goal is to help you understand how to apply genetics to your diet and lifestyle decisions. Debbie has a BS in engineering and an MSc in biological sciences from Clemson University. Debbie combines an engineering mindset with a biological systems approach to help you understand how genetic differences impact your optimal health.