The polymorphic nature of the cytochrome P450 (CYP) genes affects individual drug
response and adverse reactions to a great extent. This variation includes copy number
variants (CNV), missense mutations, insertions and deletions, and mutations affecting
gene expression and activity of mainly CYP2A6, CYP2B6, CYP2C9, CYP2C19 and CYP2D6,
which have been extensively studied and well characterized. CYP1A2 and CYP3A4 expression
varies significantly, and the cause has been suggested to be mainly of genetic origin
but the exact molecular basis remains unknown. We present a review of the major polymorphic
CYP alleles and conclude that this variability is of greatest importance for treatment
with several antidepressants, antipsychotics, antiulcer drugs, anti-HIV drugs, anticoagulants,
antidiabetics and the anticancer drug tamoxifen. We also present tables illustrating
the relative importance of specific common CYP alleles for the extent of enzyme functionality.
The field of pharmacoepigenetics has just opened, and we present recent examples wherein
gene methylation influences the expression of CYP. In addition microRNA (miRNA) regulation
of P450 has been described. Furthermore, this review updates the field with respect
to regulatory initiatives and experience of predictive pharmacogenetic investigations
in the clinics. It is concluded that the pharmacogenetic knowledge regarding CYP polymorphism
now developed to a stage where it can be implemented in drug development and in clinical
routine for specific drug treatments, thereby improving the drug response and reducing
costs for drug treatment.