Polymorphism of phase II enzymes: identification of new enzymes and polymorphic variants by database analysis

The Phase II enzymes of xenobiotic metabolism are characterized by a high l evel of substrate diversity and genetic polymorphism. Genetic polymorphism of the Phase II enzymes can be of substantial clinical significance as same variants have differences in substrate specificity, stability and levels o f expression. Variation in these factors can give rise to abnormal drug met abolism and susceptibility to carcinogens and toxins. A new approach to the discovery of additional members of Phase II enzyme families and the identi fication of polymorphic variants using searches of the EST databases has be en investigated. The examples provided demonstrate that relatively simple s earch strategies can be highly productive. (C) 1998 Elsevier Science Irelan d Ltd. All rights reserved.