This chapter discusses various aspects of clinical pharmacogenetics. In the area of pharmacology, the identification of the series of proteins in the familiar pharmacologic cascade essentially identified not only a series of targets for drugs but also a series of genetic targets that might contribute to interindividual variability in drug response. Pharmacologically, significant genetic variation has been described at every point of the cascade leading from the pharmacokinetics of drug absorption to the pharmacodynamics (PD) of drug effect. One of the most well-known polymorphisms relevant to PD response is in the aldehyde dehydrogenase gene. The gene encoding the CYP2D6 enzyme is localized on chromosome 22. By using restriction fragment length polymorphism analysis and the allele-specific polymerase chain reaction, three major mutant alleles were found in Caucasians. One of the most developed examples of clinical pharmacogenomics involves the polymorphism of thiopurine S-methyltransferase. The combined variants in drug metabolism and receptor gene are elaborated in the chapter. In the development of new pharmacogenetic tests, as for any other clinically applied test, assay sensitivity, specificity, and positive predictive value need to be scrutinized rigorously.
ASJC Scopus subject areas