Our body has built-in antioxidants that fight against cellular stress. The superoxide dismutase (SOD1) enzyme fights against oxidative stress in your cells, constantly battling to balance out oxidants with antioxidants.
Here I’ll explain how the SOD1 enzyme works and how your genes impact oxidative stress. I’ll cover how to check your genes and steps you can take if you have SOD1 variants. Members will see their genotype report below, plus additional solutions in the Lifehacks section. Join today.
SOD1: Superoxide Dismutase 1
The SOD1 gene codes for the copper-zinc superoxide dismutase enzyme. This cellular enzyme protects against oxidative stress through deactivating reactive oxygen species (ROS).
Three types of superoxide dismutases are part of our built-in antioxidant system:[ref]
- SOD1, found in the cytosol or fluid in cells
- SOD2, a mitochondrial antioxidant
- SOD3, which is extracellular or outside of the cells
SOD1 binds copper and zinc ions together and destroys free radicals. It is an antioxidant that our body produces which converts superoxide radicals into oxygen and hydrogen peroxide. Other enzymes then break down the hydrogen peroxide.
Balancing out oxidation reactions:
This is all about electrons here… Superoxide is two oxygen molecules bonded together but with one electron missing (O2−). Normal oxygen that we breathe in the air is a stable combo of two oxygen molecules. The superoxide compound, which lacks an electron, is highly reactive, wanting to bind with another molecule to balance out its charge.
SOD1 – superoxide dismutase 1 – can counteract the superoxide produced in cellular reactions.
While we often think of antioxidants being good and reactive oxygen species such as superoxide as being ‘bad’, ROS does play a vital role in cell signaling. Our cells need to be in balance with antioxidants and pro-oxidants.
Additionally, our immune system produces pro-oxidants such as superoxide to kill invading pathogens.
Balance is key, and SOD1 provides that balance.
Research on SOD1:
Research on the different genetic variants shows that SOD1 impacts heart disease risk, kidney disease, hearing loss, and diabetes. Oxidative stress plays a role in all of these chronic conditions, and decreased SOD1 (or too much ROS) can contribute to the development of these diseases.[ref][ref]
Oxidative stress seems to play a role in Alzheimer’s disease as well, and SOD1 variants have been studied to see if they affect the risk of Alzheimer’s. For rs2070424, the G allele offers protection against Alzheimer’s disease regardless of APOE gene status.[ref][ref] (Check your APOE genes if you want to know more about your Alzheimer’s risk)
Overall, higher SOD activity has links to decreased mortality in women. Oddly, this statistic didn’t hold true for men.[ref]
SOD1 in ALS:
One of the first genetic mutations linked to the familial form of ALS was in the SOD1 gene. More recent research points to misfolded SOD1 proteins being present both in the hereditary type of ALS (about 10% of ALS patients) and in the sporadic type. While there is still a lot that researchers don’t know here, it looks like the SOD1 mutations cause a gain-of-function and altered folding in a way that causes a loss of motor neuron function.[ref]
SOD1 Genotype Report
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SOD1 genetic variants can cause either an increase or a decrease in enzyme activity. Rare mutations in SOD1 have links to several diseases including an inherited form of ALS (Lou Gehrig’s disease).[ref] More common variants are linked with conditions such as diabetes, cardiovascular disease, kidney disease, and hearing damage.
Check your genetic data for rs1041740 (23andMe v4, v5; AncestryDNA):
- T/T: significantly increased risk for kidney problems in people with diabetes, increased heart disease mortality risk[ref]ref][ref]
- C/T: increased risk of kidney disease in T1D
- C/C: typical
Members: Your genotype for rs1041740 is —.
Check your genetic data for rs2070424 (23andMe v4; AncestryDNA):
- A/A: typical
- A/G: protective against Alzheimer’s Disease (OR=0.47), protective against diabetes
- G/G: higher SOD1 enzyme activity, protective against Alzheimer’s Disease (OR=0.47)[ref] protective against myelomeningocele (neural tube defect)[ref] protective against diabetes[ref]
Members: Your genotype for rs2070424 is —.
Check your genetic data for rs10432782 (23andMe v4 only):
- T/T: typical
- G/T: typical activity
- G/G: higher SOD1 enzyme activity, greater risk of noise-induced hearing loss[ref]
Members: Your genotype for rs10432782 is —.
Note: 23andMe data is not guaranteed to be clinically accurate. There is always a chance that a rare mutation is a false positive. It is recommended that you get a clinical grade test done to confirm.
Check your genetic data for i5000864 G93A (rs121912436, 23andMe v4):
- G/G: typical
- A/G: carrier of a pathogenic mutation linked to ALS[ref]
Members: Your genotype for i5000864 is —.
Check your genetic data for i5048521 (rs121912431, 23andMe v4):
- G/G: typical
- C/G: carrier of a pathogenic mutation linked to ALS[ref]
Members: Your genotype for i5048521 is —.
LifehacksThe rest of this article is for Genetic Lifehacks members only. Consider joining today to see the rest of this article.
Supplements for SOD:
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Nrf2 Pathway: Increasing the body’s ability to get rid of toxins
The Nrf2 (Nuclear factor erythroid 2–related factor) signaling pathway regulates the expression of antioxidants and phase II detoxification enzymes. This is a fundamental pathway that is important in how well your body functions. Your genetic variants impact how well this pathway functions.
Originally published 10/2015, updated 9/2020
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 also 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.