Phase II detox – GSTs

This is part of an ongoing series on the genes involved in detoxification.

Another phase II detox reaction occurs with the glutathione S-transferases enzymes, which has eight classes identified: alpha, kappa, mu, omega, pi, sigma, theta, and zeta.  The classes are abbreviated with their first letter (i.e. GSTMA for alpha).  These phase II enzymes add a glutathione to toxins in order to detoxify them.  GSTs are found in the liver, intestines, and several other places in the body and are responsible for detoxifying a large number of pesticides, herbicides, carcinogens, and chemotherapy drugs.

Once a toxic substance has been conjugated with glutathione via the GST specific enzyme, it can be excreted from the body via bile or urine.  Glutathione is considered the master antioxidant for the body.  Here is a nice article on ways to boost your glutathione level with food.

There are several fairly common polymorphisms that can decrease the function of your GSTs.  But, once again, environmental factors also play a huge role in your detox system.  So if you have non-functioning genes for a specific enzyme, your body has alternate ways to detox most substances and you can naturally boost those routes through nutrition.  One way of inducing GSTs is thought to be through cruciferous vegetable consumption.  [ref]

There have been quite a few studies done on the GST polymorphisms.  So if you find that you have one of these common polymorphisms, you may want to read up on some of the studies in PubMed.  Some studies are contradictory, and some seem to be specific to gender or ethnicity.

GSTA1 has a common polymorphism that significantly reduces its function.  When looking at research studies, GSTA1*A is the functioning enzyme, and GSTA1*B is the reduced function version.  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].  Before you stop eating broccoli all together, weigh this against cancers that are prevented by it.  GSTA1*B with higher 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 23andMe results for rs3957357:

  • A/A: GSTA1*B, low/ non-functioning enzyme
  • A/G: GSTA1*A/*B
  • G/G: GSTA1*A

 

GSTM1 has a very common (about half of some populations) mutation that is associated with little or no GSTM1 expression.  It can be found in 23andMe data through looking at rs366631 which is a SNP that has been correlated with a deletion in GSTM1.  [ref]  There are over 2500 PubMed entries for ‘GSTM1 polymorphism’, and it has been studied in reference to many different types of cancer, glaucoma, and diabetes. There is a higher risk of some cancers with non-functioning GSTM1 gene, but the association is modified for some by diet and environment.  This seems to be a mutation that should encourage people to eat healthy and not smoke!

Check your 23andMe results for rs366631:

  • A/A: GSTM1, low/ non-functioning enzyme
  • A/G: GSTM1 functioning
  • G/G: GSTM1 functioning

 

GSTP1 is another GST gene with very common polymorphisms.  It is involved in estrogen metabolism, and in a 2009 US study, the polymorphism (G/G) was found to reduce the risk of breast cancer in post-menopausal women vs. A/A [ref]. Conversely, women with GSTP1 G/G were found to have a higher risk of breast cancer in a 2008 Chinese study.  Those with the lowest intake of cruciferous vegetables with G/G were found to have the highest risk of breast cancer.  [ref]  The difference between the two studies may be ethnicity or pre- vs. post-menopausal women.

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. It is an interesting study that is worth reading.  Note though that there were only 160 participates, male only.[ref]

A study in rats in 2015 found that carnosic acid (found in rosemary) up-regulates the GSTP enzyme.  [ref] And a study in mice found that GSTP-null mice had less weight gain on a high fat diet. [ref] Another study in mice showed less acetaminophen toxicity in GSTP-null. [ref]

Check your 23andMe results for rs1695:

  • A/A: normal
  • A/G: somewhat reduced GSTP1 activity
  • G/G: somewhat reduced GSTP1 activity [ref]

 

GST/T1 is another GST with deletion or null activity being fairly common — ~20% of Caucasians and 80% of Asians.  GST/T1 null has been implicated in increased risk of several diseases: MS [ref], kidney disease from exposure to organochlorine pesticides [ref],  esophageal cancer [ref], lymphoma due to polycyclic aromatic hydrocarbons [ref], and many more.

There is no SNP that defines GST/T1 null vs present, as far as I can find.  The Genetic Genie detox report does include it.  If you go to your raw data on 23andMe and search for the GST/T1 gene, a lot of ‘no call’s should indicate GST/T1 null.

 



Author Information:   Debbie Moon
Debbie Moon is the founder of Genetic Lifehacks. She holds a Master of Science in Biological Sciences from Clemson University. Debbie is a science communicator who is passionate about explaining evidence-based health information. Her goal with Genetic Lifehacks is to bridge the gap between scientific research and the lay person's ability to utilize that information. To contact Debbie, visit the contact page.

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