Human alpha class glutathione S-transferases: genetic polymorphism, expression, and susceptibility to disease.

摘要: The human alpha class glutathione S-transferases (GSTs) consist of 5 genes, hGSTA1-hGSTA5, and 7 pseudogenes on chromosome 6p12.1-6p12.2. hGSTA1-hGSTA4 have been well characterized as proteins, but hGSTA5 has not detected a gene product. hGSTA1-1 (and to lesser extent hGSTA2-2) catalyzes the GSH-dependent detoxification carcinogenic metabolites environmental pollutants tobacco smoke (e.g., polycyclic aromatic hydrocarbon diolepoxides) several alkylating chemotherapeutic agents peroxidase activity toward fatty acid hydroperoxides (FA-OOH) phosphatidyl FA-OOH. hGSTA3-3 high for Delta(5)-Delta(4) isomerization steroids, hGSTA4-4 GSH conjugation 4-hydroxynonenal. hGSTA4 is expressed in many tissues; hGSTA2-2 are at levels liver, intestine, kidney, adrenal gland, testis; hGSTA3 steroidogenic tissues. Functional, allelic, single nucleotide polymorphisms occur an SP1-binding element hGSTA1 coding regions hGSTA2 hGSTA3. main effects these low hepatic expression individuals homozygous hGSTA1*B specific hGSTA2E-2E variant These properties suggest that GSTs will be involved susceptibility diseases with component (such cancer, asthma, cardiovascular disease) response chemotherapy. Although hGSTM1, hGSTT1, hGSTP1 associated such (on basis genetic indicators expression), little studied this respect. Nevertheless, increased colorectal cancer efficacy chemotherapy breast cancer. Methods identification quantitation GST protein, mRNA, genotype reviewed, potential GST-alpha plasma used marker induction discussed.