Genetic Variations in Human Glutathione Transferase Enzymes: Significance for Pharmacology and Toxicology

Abstract

Glutathione transferase enzymes (GSTs) catalyze reactions in which electrophiles are conjugated to the tripeptide thiol glutathione. While many GST-catalyzed transformations result in the detoxication of xenobiotics, a few substrates, such as dihaloalkanes, undergo bioactivation to reactive intermediates. Many molecular epidemiological studies have tested associations between polymorphisms (especially, deletions) of human GST genes and disease susceptibility or response to therapy. This review presents a discussion of the biochemistry of GSTs, the sources—both genetic and environmental—of interindividual variation in GST activities, and their implications for pharmaco- and toxicogenetics; particular attention is paid to the Theta class GSTs.

Effects of genetic polymorphisms of glutathione S-transferase genes (GSTM1, GSTT1, GSTP1) on the risk of diabetic nephropathy: a meta-analysis

“…The prevalence of GSTM1 homozygous null individuals in Caucasian and Asian populations is about 50%. 28 It should be noted that in 2 studies included in the meta-analysis, 1 Caucasian and 1 Asian, 21,23 the prevalence of GSTM1(-) individuals was 2-fold lower in the control group. It should be stressed that for convenience and for hypothesis testing, we decided to perform the frequency analyses starting with conventional definitions of ethnicity and being aware that, for example, the Asian population can be heterogeneous.…”

Associations of Polymorphic Variants of the Biotransformation Genes with the Components of the Glutathione System in Men with Infertility

“…(8,10,11,27,28) Antioxidants, such as GSTM1 and GSTT1, can reduce the toxic effects of OS on male germ lines, suggesting that these two antioxidants genes may play a protective role against OS in spermatogenesis. (12) Thus, the deletion polymorphisms of GSTM1 and GSTT1 are considered as candidates for genetic susceptibility factors for male infertility.…”

“…Susceptibility of the organism to adverse effects of the environment is highly dependent on the activity of the xenobiotic detoxification enzymes. (8,9) Depending on genetically determined peculiarities of xenobiotic biotransformation, its interaction with receptors and enzyme systems, detoxification enzymes define the body's reaction to various toxic substances and pharmaceuticals. (10)(11)(12)(13)(14) The glutathione S-transferase (GST) genes (GSTM1, GSTT1, and GSTP1) are involved in the detoxification of a broad range of toxic substances.…”

Research Article Synergic effect of oral contraceptives, GSTP1 polymorphisms, and high-risk HPV infection in development of cervical lesions.

“…Polymorphisms in GSTcoding sequences may allow different levels of response to environmental factors, as toxins and carcinogens, which would contribute to cancer susceptibility (Josephy, 2010).…”