PMID: 9443163Jan 27, 1998Paper

Pharmacogenetics in biological perspective

Pharmacological Reviews
W Kalow

Abstract

What have we learned? Pharmacogenetics, heritable variation in response to xenobiotics, is present in all forms of life. Initially, human data perhaps have created the most excitement, and they provide much biochemical detail. However, if we look at pharmacogenetic variation of insects and bacteria, we see it as a characteristic of populations; individuals with inborn resistance to various toxicants can cause the survival of a population by the process of Darwinian selection. Diversity of a population and Darwinian selection are different milestones serving population survival. Variation of drug response may represent variation of drug targets, drug metabolism, and probably drug transport. Metabolic variation appears to be the most prominent; at present, it is not clear whether this prominence has historical or biological causes. It is an interesting exercise to compare pharmacogenetic resistance with intoxication and resistance to infection by invasion of disease-carrying bacteria or other pathogens. The big difference is that pathogens tend to show variabilities that drugs do not have. The immune system is made to deal with the genetic variabilities linked to the short life span of most pathogens. However, there are, besides ...Continue Reading

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