Detox pathway and genes that impact the GST system
Insights into the body’s detox ability may be determined by uploading DNA raw data from genetic testing companies like 23andMe to identify the GST gene variant carried. The GST genes are responsible for synthesizing and recycling glutathione.
The glutathione/GST system is one of the body’s most important detox mechanism, which lowers oxidative stress and plays an important role in DNA repair, immunity and detoxification of chemicals, metals and estrogens.
The enzymes that belong to the family of glutathione S-transferase (GST) and cytochrome P450 (CYP) families are associated with a two-stage detoxification process for multiple toxins and potential carcinogens. Phase I enzymes act on most potentially toxic compounds and then these activated metabolites undergo detoxification by phase II enzymes, especially GST.
There are eight classes of the GST enzyme, from alpha to zeta (names GSTA, GSTM etc). These enzymes detoxify toxins by adding a glutathione and are found mainly in the liver but are also found in other parts of the body like the intestine.
Mechanism of action of the GST enzyme- Detoxification
Any toxin that has been conjugated with glutathione by the GST enzyme is then removed from the body in the urine or in the bile.
Phase I and Phase II detoxification system and risk of disease
Research studies have shown that phase I and phase II gene polymorphisms are associated with the risk for the following diseases
- GST gene polymorphism and Cancer risk: Studies on GST gene polymorphism indicated increased risk for breast cancer, bladder cancer and other types of cancer, based on the variant carried.
- GST gene polymorphism and Coronary artery disease: A meta analysis of studies was conducted which included 19 studies, with 8020 cases and 11 501 controls. The study conducted in 2010 showed that there was an increase in coronary heart disease among individuals with certain variants of the gene.
- GST gene polymorphism and Type 2 diabetes: A study conducted in 2015 showed that GST gene polymorphisms were associated with an increased risk for type 2 diabetes. 84 patients were included in the study that also included 108 controls.
- GST gene polymorphism and Miscarriage: A study conducted in 2010 showed that women who carried certain genetic variants were associated with an increased risk of miscarriage. The mechanisms involved in detoxification, according to the study, could influence pregnancy outcomes. A deficient detox system could increase exposure to toxins, which may lead to early pregnancy loss.
Here are a few common polymorphisms in the GST gene that are associated with the level of glutathione transferase activity. To find out the inherited variant of GSTM1 23andme DNA raw data is all that is required. There are extensive pubmed entries for GST polymorphism and their associated disease risk.
Check your 23andMe raw data or Ancestry DNA raw data to identify which variant of rs366631 you carry.
| Genotype | Phenotype |
|---|---|
| AA | More likely to have lower enzyme activity |
| GA | More likely to have normal enzyme activity |
| GG | More likely to have normal enzyme activity |
Check your 23andme raw data or ancestry DNA raw data to identify which variant of rs3957357 you carry.
| Genotype | Phenotype |
|---|---|
| AA | More likely to have lower enzyme activity |
| GA | More likely to have normal enzyme activity |
| GG | More likely to have normal enzyme activity |
Check your 23andme raw data or ancestry DNA raw data to identify which variant of rs1695 you carry
| Genotype | Phenotype |
|---|---|
| AA | More likely to have normal enzyme activity |
| GA | More likely to have reduced enzyme activity |
| GG | More likely to have reduced enzyme activity |
There are genetic testing services like Genetic Genie detox profile which lists even GSTT1 null alleles that are present in the 23andme raw data. However, the genetic genie detox profile interpretation does not include recommendations that Xcode Detox profile does.
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