High Carrier Prevalence of Deficient and Null Alleles of CYP2 Genes in a Major USA Hospital: Implications for  Personalized Drug Safety

Abstract

Many drugs are metabolized by highly polymorphic cytochrome P450 (CYP) enzymes. Among these enzymes, members of the CYP2 family coded by the CYP2D6, CYP2C9 and CYP2C19 genes are best amenable to the precise prediction of an individual’s innate capacity to metabolize drugs by DNA typing of inherited null and deficient alleles. We determined the frequency of these alleles and the prevalence of their carriers in a New England, USA, tertiary care center to assess underlying population genetic features for the practice of personalized medicine. We determined that 54, 25 and 27% are carriers of at least one deficient or null allele for the CYP2D6, CYP2C9 and CYP2C19 genes, respectively. Furthermore, 6% of individuals are carriers of two null alleles for CYP2D6 and are predicted to have no biochemical activity for this isoenzyme. These results support the implementation of DNA typing of CYP2 genes to diagnose adverse drug reactions and to prevent a substantial number of patients being prescribed drugs they cannot adequately metabolize.

Keywords: :

• adverse drug reactions
• alleles
• CYP2C19
• CYP2C9
• CYP2D6
• DNA typing
• drug metabolism
• patient safety