GSTs: glutathione-S-transferase enzymes for detoxifying environmental toxins.

Exposure to many different man-made chemical compounds occurs every day, and our exposure to new toxicants well exceeds what our ancestors experienced. Your body has fascinating ways of breaking down and eliminating toxicants, medications, and even hormones made in the body.

Detoxification often is a two-phase process. The first step (phase I) makes the molecules more reactive and phase II (conjugation) makes the molecules ready to be bound to something. This process is then followed by elimination (urine, feces).

GSTs: phase II detoxification enzymes

The glutathione S-transferase genes code for enzymes involved in the removal of a variety of carcinogens and environmental toxins.[ref]

These phase II detoxification enzymes combine the metabolites from phase I with molecules that make them less toxic and more easily excreted.

There are eight different enzymes in the GST family of genes and identified by Greek letters: alpha, kappa, mu, omega, pi, sigma, theta, and zeta. As such, abbreviations for the classes start with their first letter (i.e. GSTMA for alpha).

The GST enzymes are found in the liver, intestines, and several other tissues. They are responsible for detoxifying a large number of pesticides, herbicides, carcinogens, and chemotherapy drugs.

Glutathione, an endogenous antioxidant

The GST enzymes conjugate (bind) an antioxidant called glutathione to the substance for elimination. Glutathione is considered the master antioxidant for the body.

Once a toxic substance has been conjugated with glutathione via the GST-specific enzyme, the body excretes it via bile or urine.

One very important role performed by the GST enzymes is to rid the body of polycyclic aromatic hydrocarbons (PAHs). Cigarette smoke, diesel exhaust, and grilled meats all contain PAHs. Not to mention, PAHs are known carcinogens.[ref]

In addition to its role in removing toxicants, GST enzymes are also important for neutralizing reactive oxygen species which cause oxidative stress in cells.[ref][ref]

Several fairly common genetic variants can decrease the function of the GST enzymes, but with several different GST enzymes available, often the body has a backup route for getting rid of toxicants.

Importantly, environmental factors, such as exposure to toxicants (pollution, cigarette smoke) also play a large role here. It really is a matter of genetic susceptibility along with exposure to toxins and carcinogens.


Genetic variants in the GST genes:

Genetic variants greatly impact the way that your GST genes function, with common variants causing non-functioning genes.

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GSTM1 enzyme:

The GSTM1 (glutathione S-transferase mu 1) enzyme helps the body detoxify several types of carcinogens, drugs, toxins, and oxidative stress byproducts.

Not everyone has a functioning copy of this gene, and the non-functioning (null) genotype shows links to cancer susceptibility.[ref] The deletion is fairly common with  50 – 78% of people, depending on ethnic group, having the null genotype for GSTM1.

Check your genetic data for rs366631 (23andMe v4 only):

  • A/A: deletion (null) GSTM1 gene. 2x increased risk of breast cancer[ref],  increased susceptibility to lung cancer in smokers[ref], increased risk of prostate cancer in Caucasians[ref] (common genotype in many population groups)
  • A/G: GSTM1 present
  • G/G: GSTM1 present

Members: Your genotype for rs366631 is .

 

GSTA1 gene:

A non-functioning version of the GSTA1 gene is referred to in studies as GSTA1*B.  A couple of studies show that with GSTA1*B there is a higher risk for colon cancer with high cruciferous vegetable intake, especially broccoli.[ref][ref] On the other hand, people with the GSTA1*B genotype and high cruciferous veggie consumption were found to have more protection against breast cancer.[ref]  GSTA1*B is also associated with a higher risk of asthma and allergies.[ref]

Check your genetic data for rs3957357 (23andMe v4, v5; AncestryDNA):

  • A/A: GSTA1*B, low/ non-functioning enzyme; increased risk of asthma, allergies[ref] interaction with cruciferous vegetables and cancer risk[ref][ref][ref]
  • A/G: GSTA1*A/*B, somewhat lower enzyme function.
  • G/G: GSTA1*A

Members: Your genotype for rs3957357 is .

 

GSTP1 gene:

GSTP1 is involved in estrogen metabolism, and women with GSTP1 G/G were found to have a higher risk of breast cancer in a 2008 Chinese study. This increased risk was dependent, though, on the amount of cruciferous vegetables consumed. Those with the G/G alleles and the lowest intake of cruciferous vegetables seemed to have the highest risk of breast cancer.[ref]

A 2012 study on men taking Vitamin E (alpha-tocopherol) supplements found that those with GSTP1 A/A and A/G had higher levels of inflammation (measured IL-6), while those with G/G had decreased IL-6 levels.[ref]

Check your genetic data for rs1695 (23andMe v4, v5; AncestryDNA):

  • A/A: typical; possibly higher IL-6 in men who take vitamin E[ref]
  • A/G: typical risk of breast cancer
  • G/G: reduced function, increased risk of breast cancer[ref][ref] increased risk of prostate cancer[ref] increased risk of nasal polyps[ref]

Members: Your genotype for rs1695 is .

 

GSTO1 gene:

The GSTO1 gene codes for a glutathione-S-transferase that acts a little bit differently than the rest. This enzyme reportedly plays a pro-inflammatory role in certain situations, such as bacterial infections.[ref] Additionally, it plays a role in neutralizing oxidative stress.[ref]

Check your genetic data for rs4925 (23andMe v5; AncestryDNA):

  • C/C: typical (most common);
  • A/C: lower mortality in renal cell carcinoma (males); increased susceptibility to PCOS; increased skin lesions in arsenic poisoning[ref]
  • A/A: lower mortality in renal cell carcinoma (males)[ref]; increased risk of PCOS[ref]; increased problems detoxifying arsenic

Members: Your genotype for rs4925 is .

GSTT1 gene:

Another important GST gene is the GSTT1 gene. Similar to the GSTM1 gene, some individuals have a null or deleted GSTT1 gene. While there isn’t a specific marker to check to see if you have the null variant, if you ‘browse raw data’ on your 23andMe account find that the GSTT1 gene shows a lot of “not determined” calls, you are likely to have a GSTT1 null genotype.

Lifehacks

There are several dietary ways to naturally increase the amount of the GST enzymes the body produces.

Lifestyle factors:

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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.