Recent Progress in Pharmacogenetics

Abstract

Publisher Summary This chapter discusses the hereditary factors causing clinically significant variations in human responsiveness to drugs and the substantial advances made in pharmacogenetics. Along with past much recent work that has been reviewed in the chapter is devoted to these genetically transmitted conditions, but only a few new examples have been described. In the chapter, the term pharmacogenetics is applied to clinically significant consequences of hereditary variations in the handling of drugs. The chapter deals mainly with an increasing body of data on the defects in human and only tangentially with the very large literature, concerning animal experiments. Search for hereditary variations, affecting the way the body handles drugs, has until recently turned up almost exclusively traits inherited as single factors— that is, traits produced by point mutations at a single genetic locus and transmitted, either as Mendelian dominants or recessives. Investigation of the responsiveness of the general population to a drug in terms of the amount of a drug required to produce a given effect may take the form of a continuous unimodal distribution curve or of a discontinuous polymodal curve. Until recently, studies of drug responses that yield a normal or continuous distribution curve have been almost entirely ignored in pharmacogenetic investigations. To construct unimodal, Gaussian distribution curves large populations are required. Furthermore, genotypes are hard to deduce from such curves. In contrast, discontinuous, bimodal, or trimodal curves of response obtained from disorders transmitted as Mendelian dominants or recessives are more easily analyzed because each discrete curve generally corresponds to a different genotype.