GSTM1 rs1695: Understanding the Null Genotype and Detoxification
The GSTM1 gene encodes an enzyme responsible for neutralizing environmental toxins and oxidative stress. A common genetic variation, known as the null genotype, involves a complete deletion of this gene, which may impact how individuals process certain substances.
What each genotype means
Normal enzyme activity
This genotype represents the presence of the functional GSTP1 enzyme, often referred to as the Ile105 variant. Research indicates this form of the enzyme typically exhibits higher catalytic activity compared to the G allele. If you are considering treatments involving specific medications like fumaric acid esters, please discuss your potential response profile with your clinician or pharmacist.
Carried by approximately 66% of the global population, though frequencies vary significantly by ancestry.
Intermediate enzyme activity
This heterozygous genotype results in a mix of both the highly active and less active forms of the GSTP1 enzyme. Because you carry one copy of each variant, your enzyme activity levels may be intermediate compared to those with two copies of either the A or G allele. Please consult with your healthcare provider regarding how this might influence your response to specific environmental factors or medications.
This genotype is common across most populations, reflecting the widespread distribution of both the A and G alleles.
Reduced enzyme activity
This genotype is associated with the Val105 variant, which research indicates has lower enzymatic activity than the common A allele. Some studies suggest this reduced activity may influence how your body processes certain drugs, such as fumaric acid esters used for psoriasis. Please discuss your specific medication dosing and treatment efficacy with your clinician or pharmacist.
Carried by roughly 34% of the global population, with lower frequencies observed in East Asian populations.
What is the GSTM1 Null Variant?
The GSTM1 gene is located on chromosome 1. The variant often referred to as the null genotype is not a single nucleotide polymorphism in the traditional sense of a base-pair swap, but rather a structural variation involving a large-scale deletion of the gene. When an individual carries this deletion on both copies of their chromosomes, they are unable to produce the functional glutathione S-transferase mu 1 enzyme. This complete absence of the enzyme is what researchers describe as the null genotype. Because this deletion removes the entire coding sequence, it results in a total loss of the specific detoxification activity associated with this protein. Scientists study this variant to understand how genetic differences in metabolic pathways might influence individual responses to environmental exposures and pharmacological agents.
The Role of GSTM1 in Detoxification
Glutathione S-transferases are a family of enzymes that play a critical role in cellular defense. Specifically, the GSTM1 enzyme helps the body neutralize reactive oxygen species and detoxify various harmful compounds, including those found in tobacco smoke and certain environmental pollutants. By attaching glutathione to these toxic molecules, the enzyme makes them more water-soluble and easier for the body to eliminate. When the GSTM1 enzyme is absent due to the null genotype, the body's capacity to manage oxidative stress and clear these specific toxins may be reduced. Research suggests that this reduced capacity could potentially lead to higher levels of cellular stress, which is why scientists have investigated its role in various health conditions, ranging from chronic inflammation to susceptibility to certain cancers.
Research Associations and Evidence
The scientific literature contains hundreds of studies examining the GSTM1 null genotype. Research has explored its potential association with an increased risk for various conditions, including lung, bladder, and prostate cancers, particularly in individuals with high exposure to tobacco smoke. Additionally, some studies have linked the null genotype to an increased incidence of drug-induced liver injury and higher levels of oxidative stress in patients with chronic kidney disease. However, it is important to note that the evidence is often mixed or moderate in strength. Many of these associations are complex and likely depend on interactions with other genes, lifestyle factors, and environmental exposures. Because these findings are based on statistical correlations across large populations, they cannot predict an individual's specific health outcome or disease risk.
What You Can and Cannot Do With This Information
Understanding your GSTM1 status is primarily for educational purposes. Because the null genotype is very common, it is considered a normal variation in human genetics rather than a rare disease-causing mutation. You cannot use this information to diagnose yourself with any condition or to predict your future health with certainty. If you are concerned about how your genetics might influence your response to a specific medication, it is essential to discuss this with your clinician or pharmacist. They are the only ones qualified to interpret your genetic information in the context of your overall health history and current treatment plan. Avoid making any changes to your medications or lifestyle based solely on genetic test results without professional medical guidance.
How common is this variant?
The GSTM1 null genotype is highly prevalent, found in approximately 40-60% of many populations worldwide, with significant variation observed across different ethnic groups.
Frequently asked questions
Is the GSTM1 null genotype a disease?
No, the GSTM1 null genotype is not a disease. It is a common genetic variation found in a large portion of the healthy population.
Does having the null genotype mean I will get cancer?
No. While some studies suggest a statistical association between the null genotype and certain cancer risks, it is only one of many factors. Lifestyle, environment, and other genetic factors play much larger roles in overall health.
Should I get tested for the GSTM1 null genotype?
There is currently no standard clinical recommendation to test for this variant. Genetic testing for GSTM1 is not typically used to guide routine medical care.
Can I increase my GSTM1 enzyme activity if I have the null genotype?
If you have the null genotype, you do not have the gene to produce the enzyme. Therefore, you cannot increase its activity through diet or supplements.
Sources & further reading
Educational information only, last refreshed 10/2/2026. Not medical advice — these associations describe population statistics, not individual predictions.
Curious what your genotype is for rs1695?
Upload a raw DNA file from 23andMe, AncestryDNA, MyHeritage, or FamilyTreeDNA and see this variant — plus thousands more — interpreted in your full report.
Get my report — $29Related variants in GSTM1
A well-studied variant within the glutathione S-transferase family linked to susceptibility to hypertension and vascular disease.
Single-nucleotide polymorphism tagging glutathione S-transferase M1 functional status, influencing xenobiotic detoxification and chemotherapy efficacy/toxicity.