Glutathione s-transferases

In the human liver, GST represent up to 4% of soluble proteins and catalyze the attachment of glutathione to a variety of potentially genotoxic xenobiotics. They also detoxify carcinogenic polycyclic aromatic compounds, hydroxyl radicals, singular hydrogen and hydrogen peroxides ( ROS ).

Numerous polymorphisms have been found in the GST genes. These polymorphisms usually lead to enzymes with reduced or absent activity.

Gene deletion genotypes have been described for GST-M1 and GST-T1. People who carry a homozygous deletion of GST-M1 or GST-T1, so-called "null genotypes", lack a functioning GST-M1 or GST-T1 protein.

People with reduced GST activity react differently to environmental toxins or carcinogens (increased risk of somatic mutations and potential tumor induction - proven in head and neck tumors).

Coincidences between GST genotype (GSTM1 mutation) and e.g. head and neck carcinomas have been found.

A correlation between GST polymorphisms and reduced response to chemotherapy was observed.

Furthermore, there is an increased risk of contact allergy for GST null variants (see Genetics of contact allergy below).

The frequency of so-called zero genotypes for Caucasians is 50% for GST-M1 and about 20% for GST-T1.

1. Matthias C et al (1998) Influence of gene polymorphisms in the detoxifying enzymes of glutathione S-transferases on the chromosomal stability of squamous cell carcinomas of the head and neck. Laryngo-Rhino-Otol 77: 201-206
2. Schnuch A (2011) Genetics of contact allergy. dermatologist 62:732-738