Health & Wellness: DNA Methylation

DNA Methylation 

DNA methylation is a very important factor in our biochemical pathways. Methylation uses a process of donating methyl groups to a substrate. These methyl group substrates contain DNA and RNA, chemicals, neurotransmitters, hormones, and immune cells. A few examples of methylation include: regulating gene expression, biotransformation, myelination which is the production of the protective coating that surrounds our nerves), building neurotransmitters, immune cells, processing hormones, and DNA/RNA synthesis. 

Methylation is also involved in energy production and T-Cell production to fight infections and viruses along with regulating the immune responses of the body. B Vitamins are the main building blocks for cell growth and development. Additionally, we depend on B vitamins to protect our cells and DNA from daily damage and wear and tear. One B vitamin that is specifically essential is folate. Folate is water-soluble and low folate levels along with SNPs are associated with increased risks for chronic health conditions. We are able to test our patients and their genetic predisposition with a DNA Health test from DNA Life. A sample report is shown below: 

Genes 

MTHFD1 

This gene codes for a protein that has three different enzymatic activities. These enzymatic reactions function in the interconversion of 1-carbon derivates of tetrahydrofolate, which are substrates for methionine, thymidylate, and de novo purine syntheses. Variations of this gene are known to depress rates of de novo thymidylate synthesis, elevate uracil levels in human DNA, and increase the instability of the human genome. If one has the wild type, GG, there is no impact. If one has the heterozygous type, GA, they have a moderate impact, and if one has the homozygous type, AA, they have a high impact. 

We have seen that those with an A allele are associated with decreased enzyme activity that leads to a higher load on the folate-dependent pathway. With the GA and AA genotype, individuals have an increased risk of choline deficiency that can lead to liver and muscle dysfunction. 

For those who possess an A allele, we recommend eating foods higher in choline such as eggs, beef, and salmon. For more information, please refer to GeneCards, The Human Gene Database for MTHFD1. 

MTHFR

Methylenetetrahydrofolate reductase is a riboflavin-dependent (FAD) enzyme. This enzyme catalyzes the NADPH-dependent reduction and is a key enzyme in the folate metabolism pathways. Its main job is to direct folate to DNA synthesis or homocysteine remethylation. There are multiple gene impacts for this specific SNP. The first SNP is seen at 677 C>T. Those with a CC genotype have no impact, the heterozygote of CT have moderate, and the homozygous TT have a high impact. In this instance, the T allele reduces the stability and lowers the activity of the MTHFR enzyme. This leads to increased levels of homocysteine and a decrease in DNA methylation. For those who have a T allele, they will need to increase their folate and vitamin B uptake as their requirements are more. 

The second SNP is 1298 A>C. Those with the AA wild type have no impact. The AC heterozygote have a low impact and the CC homozygote have a moderate impact. With this, we see that the C allele affects enzyme regulation by SAMe and can be linked to decreased enzyme activity. The recommendations for these patients is the same as above in addition to reducing alcohol intake.  For more information, please refer to GeneCards, The Human Gene Database for MTHFR. 

MTRR

Methionine Synthase Reductase is involved in the reductive regeneration of vitamin B12. It’s main function is to maintain an intracellular pool of methionine as well as maintain homocysteine concentrations at non-toxic levels. Those who have a wild type AA genotype have no impact, those with a AG heterozygous genotype have a low impact and those with the GG homozygote genotype has a moderate impact. With this, we see that the G allele is connected with an increased risk for premature coronary artery disease. Additionally, having a GG genotype is a significant risk factor for the development of neural tube defects when the vitamin b12 levels are low. 

For those who have a G allele we recommended they supplement with the active form of folate, 5-methyltetrahydrofolate/5-MTHF, as well as b2, b12, and b6, especially when pregnant or trying to conceive. 

For more information, please refer to GeneCards, The Human Gene Database for MTRR. 

MTR

Methionine synthase is an enzyme that is encoded by MTR. This reaction is vitamin B12 dependent and its activity is essential to supply the methionine for SAM synthesis. With this, we see a common polymorphism that affects the functional site of the protein. This increases the levels of circulating folate and homocysteine. The AA wild type has no impact, the AG heterozygote has a beneficial impact as well as the homozygous GG genotype. 

The G allele has been linked to decreased levels of homocysteine and the SNP actually increases the activity of the enzyme that converts homocysteine to methionine. 

With this SNP, we encourage adequate vitamin b intake to better support the enzymatic activity occurring.  For more information, please refer to GeneCards, The Human Gene Database for MTR. 

CBS 

CBS is also a vitamin B dependent enzyme that is responsible for the irreversible conversion of homocysteine to cystathionine and removes homocysteine from the methionine cycle. When there are alterations we often see a change in homocysteine levels. Those who possess the wild type CC genotype, there is no impact. For those with the heterozygous CT we see a low impact and those with the TT homozygous have a moderate impact. Those with this variant allele have a decreased risk of coronary artery disease and show an increased response to the homocysteine-lowering effects that folate has. 

We recommend that patients have an adequate amount of folate. For more information, please refer to GeneCards, The Human Gene Database for CBS. 

COMT 

COMT catalyzes the transfer of a methyl group from S-adenosylmethionine to catecholamine. This includes neurotransmitters such as dopamine, epinephrine, and norephedrine. A variation of the COMT gene reduces the activity of the enzyme and should be taken very seriously as variations have been associated with breast cancer, ovarian cancer, substance use disorder, and mental disorders including schizophrenia, anxiety, bipolar, and depressive episodes. Those who have the wild type of GG show no impact. Those with the heterozygous GA show a moderate increase and those with the AA homozygous genotype show a high impact. For those who have the A allele, we see a high decrease in methylation activity. 

For patients who possess an A or G allele, we want to ensure they have methylating agents in their diet. These include supplements such as folate, b12, and SAMe. Additionally, we want to ensure that they reduce their amount of daily stress and increase their vegetable intake. For more information, please refer to GeneCards, The Human Gene Database for COMT. 

Lab Pairing

It is highly important that we ensure our patients have adequate vitamin B levels and they are using their energy efficiently. To best assess this, we use the micronutrient test by Spectracell. A sample report is shown below: 

Additionally, it is important to remember that we are not changing our genes, but rather modifying their expression. With our environmental factors, we have the ability to see our genetic predisposition and make a positive impact on their expression, ultimately leading to reduced inflammation and susceptibility to various health conditions. In this study, we see the influence of epigenetics, and especially of DNA methylation and the available knowledge in the literature on the characterization of DNA methylation profiles during skeletal muscle aging and the possible impact of physical activity and nutrition. Please read the study below:

Age-Related DNA Methylation Changes: Potential Impact on Skeletal Muscle Aging in Humans. 

As we grow up, we are constantly told to eat our vegetables and take our vitamins. However, many of us do not understand why. We just know that it is to be “healthy”. As we age, we often eat less vegetables and the majority of young adults do not take vitamins or supplements. It is critical that we are educating not only ourselves, but our children why vitamins are vegetables are so important. Without them, we do not properly feed our cells and our biochemical processes get thrown off! Specifically, if you have one of these SNPs mentioned above, it is critical that we feed your body with the proper nutrients. -Kenna Vaughn, Senior Health Coach. 

References:

 Gensous N, Bacalini MG, Franceschi C, Meskers CGM, Maier AB, Garagnani P. Age-Related DNA Methylation Changes: Potential Impact on Skeletal Muscle Aging in Humans. Front Physiol. 2019;10:996. Published 2019 Aug 2. doi:10.3389/fphys.2019.00996

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