Pharmacogenetics

Abstract

Pharmacogenetics, a term recognized in pharmacology in the pre-genomic era, is the study of the influence 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 influence 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 differences with small variability among patients 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 efficacy 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 influence in drug response and efficacy and remain constant throughout life. This has led to the recognition of the discipline “pharmacogenetics” since the 1950s, which can be viewed as an integration of gene profiling and pharmaceutical chemistry. From this initial definition, the scope has broadened so that it overlaps with pharmacogenomics.