Join Here   |   Log In

COMT Gene: Neurotransmitter levels and estrogen metabolism.

Having trouble with supplements containing methyl groups? Wondering why your neurotransmitters are out of balance? It could be due to your COMT genetic variants. COMT is an important enzyme tasked with breaking down neurotransmitters, such as dopamine.

This article explains the COMT enzyme and how to check your genetic data for COMT fast and slow polymorphisms on 23 and Me, AncestryDNA, or similar data.

What does the COMT gene do?

The COMT gene encodes the catechol-O-methyltransferase enzyme, which breaks down (metabolizes) the neurotransmitters dopamine, epinephrine, and norepinephrine. It controls the amount of neurotransmitters available. It is also involved in the metabolism of estrogen metabolites, as well as certain supplements.

Diggin deeper: 
COMT adds a methyl group from SAMe to the dopamine, epinephrine, or norepinephrine molecules. This additional methyl group changes the original molecule into a different substance, which can be eliminated or recycled in the cells.

image showing comt enzyme function converting catecholamines into inactive metabolites

Drug and supplement metabolism:
COMT also breaks down some drugs used for asthma, Parkinson’s, and high blood pressure. It is also involved in metabolizing natural supplements like curcumin and quercetin.

Estrogen:
Additionally, COMT is important in the phase II metabolism of estrogens. It converts estrogen metabolites into forms that can be excreted easily.

COMT Mutation and Altered Neurotransmitter levels

Several common genetic variants in the COMT gene alter how the enzyme functions. Some variants increase the speed at which the enzyme metabolizes neurotransmitters, and other variants can slow down the enzyme.

Terminology Explainer: The common variants that everyone looks at for COMT are technically polymorphisms (common changes in a gene) instead of mutations (rare changes). You’ll also see it referred to as a SNP, which stands for single nucleotide polymorphism.

The COMT enzyme is active in the prefrontal cortex, which is the brain region involved in planning, complex behaviors, and personality.

Researchers link COMT genetic variants to quite a variety of different diseases, from mood disorders to heart disease, possibly due to the COMT variants metabolizing neurotransmitters at different rates.

COMT
Synaptic cleft showing neurotransmitters

Psychiatric or mood disorders and COMT SNPs:

Some of the psychiatric disorders with increased risk associated with COMT genetic variants include:

  • schizophrenia[ref][ref]
  • depression[ref]
  • anxiety (in some groups)
  • bipolar disorder 

The COMT variants do not cause these disorders alone. They simply add to the susceptibility.

Estrogen dominance and COMT:

COMT is also important outside of the realm of neurotransmitters. Since it also breaks down estrogens, there are differences in the amount of COMT available in the prefrontal cortex between males and females after puberty.[ref][ref]

For example, higher levels of estrogen can decrease COMT, leading to an increase in dopamine in female brains.[ref]

Is the Val158Met SNP “bad”?

One of the well-studied COMT genetic variants is known as Val1158Met or rs4680. This variant affects the speed at which the enzyme functions.

Also, known as COMT rs4680, the A/A or Met/Met variant is found in almost 20% of the population. The slightly more common G/G or Val/Val variant occurs in 35-40% of the population.[ref]

There is a lot written online about COMT – from Facebook groups to healthcare gurus selling supplements.

Often the information leads you to believe that carrying one of the other COMT rs4860 alleles is really bad! This simply isn’t true. Research shows there are both positive and negative effects of the variant.

Instead of one allele being bad and one being good (red or green, plus or minus), studies show these common variants just add to our uniqueness. I suggest looking at the various interactions between your genotype and supplements or lifestyle factors. Use your genetic information to optimize your health – mental and physical.


COMT Genotype Report

Members: Log in to see your data below.
Not a member? Join here.
Why is this section is now only for members? Here’s why…

Member Content:

  Log In


Why join Genetic Lifehacks?

~ Membership supports Genetic Lifehack's goal of explaining the latest health and genetics research.
~ It gives you access to the full article, including the Genotype and Lifehacks sections.
~ You'll see your genetic data in the articles and reports.

Join Here


Lifehacks:

Methyl Donor Supplements:

Clinicians often suggest that those with the rs4680 A/A genotype (slow COMT) avoid going overboard with foods and supplements considered methyl donors. Methyl donors include methylcobalamin (methyl-B12), TMG, SAMe, theanine, and choline.[ref]

The logic behind this suggestion is that overwhelming the pathway with too many methyl groups can lead to a sudden rise and subsequent fall in dopamine levels — causing mood swings, anger, or anxiety.

Related article specific to this topic: Supplement Interactions and COMT

The rest of this article is for Genetic Lifehacks members only. Consider joining today to see the rest of this article.

Member Content:

  Log In


Why join Genetic Lifehacks?

~ Membership supports Genetic Lifehack's goal of explaining the latest health and genetics research.
~ It gives you access to the full article, including the Genotype and Lifehacks sections.
~ You'll see your genetic data in the articles and reports.

Join Here


Related Articles and Topics:

Mast cells: MCAS, genetics, and solutions
Mast Cell Activation Syndrome, or MCAS, is a recently recognized disease involving mast cells that misbehave in various ways. Symptoms of MCAS can include abdominal pain, nausea, itching, flushing, hives, headaches, heart palpitations, anxiety, brain fog, and anaphylaxis. Dive into the research on mast cells, genetics, and solutions.

Bipolar Disorder, Depression, Circadian Clock Genes
New research shows that depression and bipolar disorder are linked to changes or disruptions in circadian genes. Some people carry genetic variants in the circadian genes that make them more susceptible to circadian disruption.

Tryptophan
Tryptophan is an amino acid that the body uses to make serotonin and melatonin. Genetic variants can impact the amount of tryptophan that is used for serotonin. This can influence mood, sleep, neurotransmitters, and immune response.

 

References:

Bastos, Pedro, et al. “Effect of a Natural Mineral-Rich Water on Catechol-O-Methyltransferase Function.” Magnesium Research, vol. 27, no. 3, Sept. 2014, pp. 131–41. PubMed, https://doi.org/10.1684/mrh.2014.0369.

Behbahani, Parisima, et al. “Association Study of Single Nucleotide Polymorphism Rs165599 of COMT Gene, with Schizophrenia and Bipolar Mood Disorder in the South-West of Iran.” Molecular Biology Research Communications, vol. 4, no. 2, June 2015, pp. 67–72. PubMed Central, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5019293/.

Caspi, Avshalom, et al. “Moderation of the Effect of Adolescent-Onset Cannabis Use on Adult Psychosis by a Functional Polymorphism in the Catechol-O-Methyltransferase Gene: Longitudinal Evidence of a Gene X Environment Interaction.” Biological Psychiatry, vol. 57, no. 10, May 2005, pp. 1117–27. PubMed, https://doi.org/10.1016/j.biopsych.2005.01.026.

Chao, Jian-Kang, et al. “A Gender-Specific COMT Haplotype Contributes to Risk Modulation Rather than Disease Severity of Major Depressive Disorder in a Chinese Population.” Journal of Affective Disorders, vol. 246, Mar. 2019, pp. 376–86. PubMed, https://doi.org/10.1016/j.jad.2018.12.088.

Chen, Jingshan, et al. “Functional Analysis of Genetic Variation in Catechol-O-Methyltransferase (COMT): Effects on MRNA, Protein, and Enzyme Activity in Postmortem Human Brain.” American Journal of Human Genetics, vol. 75, no. 5, Nov. 2004, pp. 807–21. PubMed, https://doi.org/10.1086/425589.

COMT Gene: MedlinePlus Genetics. https://medlineplus.gov/genetics/gene/comt/. Accessed 21 Oct. 2022.

de Castro-Catala, Marta, et al. “COMT-by-Sex Interaction Effect on Psychosis Proneness.” BioMed Research International, vol. 2015, 2015, p. 829237. PubMed Central, https://doi.org/10.1155/2015/829237.

Gruber, Helen E., et al. “A Novel Catechol-O-Methyltransferase Variant Associated with Human Disc Degeneration.” International Journal of Medical Sciences, vol. 11, no. 7, 2014, pp. 748–53. PubMed, https://doi.org/10.7150/ijms.8770.

Hettema, John M., et al. “COMT Contributes to Genetic Susceptibility Shared Among Anxiety Spectrum Phenotypes.” Biological Psychiatry, vol. 64, no. 4, Aug. 2008, pp. 302–10. PubMed Central, https://doi.org/10.1016/j.biopsych.2008.03.014.

Hirata, Hiroshi, et al. “COMT Polymorphisms Affecting Protein Expression Are Risk Factors for Endometrial Cancer.” Molecular Carcinogenesis, vol. 47, no. 10, Oct. 2008, pp. 768–74. PubMed, https://doi.org/10.1002/mc.20432.

Hursel, Rick, et al. “The Role of Catechol-O-Methyl Transferase Val(108/158)Met Polymorphism (Rs4680) in the Effect of Green Tea on Resting Energy Expenditure and Fat Oxidation: A Pilot Study.” PloS One, vol. 9, no. 9, 2014, p. e106220. PubMed, https://doi.org/10.1371/journal.pone.0106220.

Kanasaki, Megumi, et al. “Deficiency in Catechol-o-Methyltransferase Is Linked to a Disruption of Glucose Homeostasis in Mice.” Scientific Reports, vol. 7, no. 1, Aug. 2017, p. 7927. PubMed, https://doi.org/10.1038/s41598-017-08513-w.

Ko, Maung Kyi Chan, et al. “Association of COMT Gene Polymorphisms with Systemic Atherosclerosis in Elderly Japanese.” Journal of Atherosclerosis and Thrombosis, vol. 19, no. 6, 2012, pp. 552–58. PubMed, https://doi.org/10.5551/jat.11254.

Kotyuk, Eszter, et al. “A Genetic Variant (COMT) Coding Dopaminergic Activity Predicts Personality Traits in Healthy Elderly.” Personality and Individual Differences, vol. 82, Aug. 2015, pp. 61–66. PubMed, https://doi.org/10.1016/j.paid.2015.03.012.

Lachman, H. M., et al. “Human Catechol-O-Methyltransferase Pharmacogenetics: Description of a Functional Polymorphism and Its Potential Application to Neuropsychiatric Disorders.” Pharmacogenetics, vol. 6, no. 3, June 1996, pp. 243–50. PubMed, https://doi.org/10.1097/00008571-199606000-00007.

Li, Wanjun, et al. “Pain in Parkinson’s Disease Associated with COMT Gene Polymorphisms.” Behavioural Neurology, vol. 2014, 2014, p. 304203. PubMed, https://doi.org/10.1155/2014/304203.

Morozova, Anna, et al. “Association of Rs4680 COMT, Rs6280 DRD3, and Rs7322347 5HT2A With Clinical Features of Youth-Onset Schizophrenia.” Frontiers in Psychiatry, vol. 10, 2019, p. 830. PubMed, https://doi.org/10.3389/fpsyt.2019.00830.

Nackley, Andrea G., et al. “Low Enzymatic Activity Haplotypes of the Human Catechol-O-Methyltransferase Gene: Enrichment for Marker SNPs.” PLoS ONE, vol. 4, no. 4, Apr. 2009, p. e5237. PubMed Central, https://doi.org/10.1371/journal.pone.0005237.

Omair, Ahmad, et al. “Genetic Contribution of Catechol-O-Methyltransferase Variants in Treatment Outcome of Low Back Pain: A Prospective Genetic Association Study.” BMC Musculoskeletal Disorders, vol. 13, May 2012, p. 76. PubMed Central, https://doi.org/10.1186/1471-2474-13-76.

Sagud, Marina, et al. “Haplotypic and Genotypic Association of Catechol-O-Methyltransferase Rs4680 and Rs4818 Polymorphisms and Treatment Resistance in Schizophrenia.” Frontiers in Pharmacology, vol. 9, July 2018, p. 705. PubMed Central, https://doi.org/10.3389/fphar.2018.00705.

Sannino, S., et al. “Adolescence Is the Starting Point of Sex-Dichotomous COMT Genetic Effects.” Translational Psychiatry, vol. 7, no. 5, May 2017, p. e1141. PubMed Central, https://doi.org/10.1038/tp.2017.109.

Shorter, Kimberly R., et al. “Consequences of Dietary Methyl Donor Supplements: Is More Always Better?” Progress in Biophysics and Molecular Biology, vol. 118, no. 1, July 2015, pp. 14–20. ScienceDirect, https://doi.org/10.1016/j.pbiomolbio.2015.03.007.

Tan, E. C., et al. “Common Variants of Catechol-O-Methyltransferase Influence Patient-Controlled Analgesia Usage and Postoperative Pain in Patients Undergoing Total Hysterectomy.” The Pharmacogenomics Journal, vol. 16, no. 2, Apr. 2016, pp. 186–92. PubMed, https://doi.org/10.1038/tpj.2015.33.

Tunbridge, Elizabeth M., et al. “Polymorphisms in the Catechol-O-Methyltransferase (COMT) Gene Influence Plasma Total Homocysteine Levels.” American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, vol. 147B, no. 6, Sept. 2008, pp. 996–99. DOI.org (Crossref), https://doi.org/10.1002/ajmg.b.30700.

van Duursen, Majorie B. M., et al. “Phytochemicals Inhibit Catechol-O-Methyltransferase Activity in Cytosolic Fractions from Healthy Human Mammary Tissues: Implications for Catechol Estrogen-Induced DNA Damage.” Toxicological Sciences: An Official Journal of the Society of Toxicology, vol. 81, no. 2, Oct. 2004, pp. 316–24. PubMed, https://doi.org/10.1093/toxsci/kfh216.

Wang, Liang-Jen, et al. “A Potential Interaction between COMT and MTHFR Genetic Variants in Han Chinese Patients with Bipolar II Disorder.” Scientific Reports, vol. 5, Mar. 2015, p. 8813. PubMed Central, https://doi.org/10.1038/srep08813.

Wichers, Marieke, et al. “The Catechol-O-Methyl Transferase Val158Met Polymorphism and Experience of Reward in the Flow of Daily Life.” Neuropsychopharmacology, vol. 33, no. 13, Dec. 2008, pp. 3030–36. www.nature.com, https://doi.org/10.1038/sj.npp.1301520.

“WikiGenes – Collaborative Publishing.” WikiGenes – Collaborative Publishing, http://www.wikigenes.org/. Accessed 21 Oct. 2022.

Woods, James S., et al. “Genetic Polymorphisms of Catechol-O-Methyltransferase Modify the Neurobehavioral Effects of Mercury in Children.” Journal of Toxicology and Environmental Health. Part a, vol. 77, no. 6, Jan. 2014, pp. 293–312. PubMed Central, https://doi.org/10.1080/15287394.2014.867210.

Xiao, Qin, et al. “Roles of Functional Catechol-O-Methyltransferase Genotypes in Chinese Patients with Parkinson’s Disease.” Translational Neurodegeneration, vol. 6, Apr. 2017, p. 11. PubMed Central, https://doi.org/10.1186/s40035-017-0081-9.


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 from Colorado School of Mines 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.