Cytochrome P450 polymorphism: From evolution to clinical use.

Abstract

The cytochromes P450s can be divided in two groups, those of high importance for endogenous functions being evolutionary quite stable and those participating in detoxification of drugs and other xenobiotics having less important endogenous functions. In the latter group extensive genetic diversity has been allowed and in addition this is of high importance for survival in different environments. The genetic polymorphisms in these genes have evolved to some extent based on dietary restrictions and environmental factors and have not been subject of conservation due to less importance for survival. In cases of high dietary selection events, gene multiplication and amplification events have been seen. The different variants in genes encoding drug metabolizing enzymes can be used as genetic biomarkers (pharmacogenomic labels) for adjustment of drug treatment leading to less adverse drug reactions and better response. Indeed, this has improved the use of personalized medicine, although the missing heredity seen based on twin studies indicates that there are indeed many more genetic variants to be discovered before one can achieve a satisfactory relationship between genotype and phenotype with respect to drug metabolism and toxicity.