The hereditary transmission of the glutathione transferase hGSTT1-1 conjugator phenotype in a large family

The polymorphism of human glutathione transferase hGSTT1-1 is expressed in three phenotypes. Experimentally, individuals can be classified as non-conj ugators:, low conjugators and 'high' conjugators depending on the enzyme ac tivity in blood towards methylene chloride using a gas chromatographic assa y. Non-conjugators do not have a functional hGSTT1 gene; however, little is known about the molecular basis of the three conjugator phenotypes. The hi gher hGSTT1-1 activity in high conjugators may be the result of enzyme indu ction or be genetically determined. Twenty-nine members of a large family, including three generations were phenotyped and genotyped with respect to h GSTT1-1. The hGSTT1-1 enzyme activity of high conjugators was twice as high as that of low conjugators, The distribution of hGSTT1-1 phenotypes strong ly indicates a Mendelian intermediary inheritance, in which a gene-dosage e ffect results in a doubled enzyme expression in the presence of two functio nal alleles, The Mendelian intermediary inheritance is further supported by the findings of a semiquantitative polymerase chain reaction method design ed to distinguish the three genotypes of hGSTT1 for rapid screening of larg e study groups. Pharmacogenetics 9:251-256 (C) 1999 Lippincott Williams & W ilkins.