Abstract
This chapter discusses the genetic polymorphism of debrisoquine oxidation. The debrisoquine/sparteine-type polymorphism is a clinically important genetic variation of drug metabolism characterized by two phenotypes, the extensive metabolizer (EM) and the poor metabolizer (PM). The PM phenotype is inherited as an autosomal recessive trait. Defective drug metabolism is due to the absence or marked decrease of cytochrome P450IID6 in the liver of most PM individuals. The discovery of restriction fragment length polymorphisms (RFLPs) led to the identification of three mutant alleles that are associated with the PM phenotype: with the XbaI restriction endonuclease, these are the alleles reflected by 44 kilobase (kb), 11.5 kb, and 16 + 9 kb fragments. Two additional mutant alleles, designated 29A and 29B, have been identified and sequenced.
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