Human glutathione S-transferase theta (GSTT1) : cDNA cloning and the characterization of a genetic polymorphism

• Published in: Biochemical journal Vol. 300; no. 1; pp. 271 - 276
• Main Authors: PEMBLE, S, SCHROEDER, K. R, SPENCER, S. R, MEYER, D. J, HALLIER, E, BOLT, H. M, KETTERER, B, TAYLOR, J. B
• Format: Journal Article
• Language: English
• Published: Colchester Portland Press 15-05-1994
• Subjects: Amino Acid Sequence; Animals; Base Sequence; Biological and medical sciences; Cloning, Molecular; DNA, Complementary; Fundamental and applied biological sciences. Psychology; Genes. Genome; Glutathione Transferase - genetics; Humans; Isoenzymes - genetics; Molecular and cellular biology; Molecular genetics; Molecular Sequence Data; Polymorphism, Genetic; Rats; Human; Nucleotide sequence; Enzyme; Isozyme; Transferases; Red blood cell; Detoxication; Phenotype; Complementary DNA; Glutathione transferase; Molecular cloning; Structural analysis; Halogen Organic compounds; Polymorphism
• ISSN: 0264-6021; 1470-8728
• DOI: 10.1042/bj3000271

In humans, glutathione-dependent conjugation of halomethanes is polymorphic, with 60% of the population classed as conjugators and 40% as non-conjugators. We report the characterization of the genetic polymorphism causing the phenotypic difference. We have isolated a cDNA that encodes a human class Theta GST (GSTT1) and which shares 82% sequence identity with rat class Theta GST5-5. From PCR and Southern blot analyses, it is shown that the GSTT1 gene is absent from 38% of the population. The presence or absence of the GSTT1 gene is coincident with the conjugator (GSST1+) and non-conjugator (GSTT1-) phenotypes respectively. The GSTT1+ phenotype can catalyse the glutathione conjugation of dichloromethane, a metabolic pathway which has been shown to be mutagenic in Salmonella typhimurium mutagenicity tester strains and is believed to be responsible for carcinogenicity of dichloromethane in the mouse. In humans, the enzyme is found in the erythrocyte and this may act as a detoxification sink. Characterization of the GSTT1 polymorphism will thus enable a more accurate assessment of human health risk from synthetic halomethanes and other industrial chemicals.