Pharmacogenetics

Abstract

Pharmacogenetics, a term recognized in pharmacology in the pre-genomic era, is the study of infl uence of genetic factors on action of drugs as opposed to genetic causes of disease. Now it is the study of the linkage between the individual's genotype and the individual's ability to metabolize a foreign compound. The pharmacological effect of a drug depends on pharmacodynamics (interaction with the target or the site of action) and pharmacokinetics (absorption, distribution and metabolism). It also covers the infl uence of various factors on these processes. Drug metabolism is one of the major determinants of drug clearance and the factor that is most often responsible for interindividual differences in pharmacokinetics. Pharmacogenetics links genotype and phenotype as shown in Fig. 4.1 .The differences in response to medications are often greater among members of a population than they are within the same person or between monozygotic twins at different times. The existence of large population differences with small intrapatient variability is consistent with inheritance as a determinant of drug response. It is estimated that genetics can account for 20-95 % of variability in drug disposition and effects. Genetic polymorphisms in drug-metabolizing enzymes, transporters, receptors, and other drug targets have been linked to interindividual differences in the effi cacy and toxicity of many medications.Although interindividual variations in drug response result from effects of age, sex, disease or drug interactions, genetic factors represent an important infl uence in drug response and effi cacy and remain constant throughout life. This has led to the recognition of the discipline "pharmacogenetics" since the 1950s, which can be viewed an as integration of gene profi ling and pharmaceutical chemistry. From this initial defi nition, the scope has broadened so that it overlaps with pharmacogenomics (see Chap. 5 ).