Polymorphic cytochrome P450 enzymes (CYPs) and their role in personalized therapy

PLoS One. 2013 Dec 10;8(12):e82562. doi: 10.1371/journal.pone.0082562. eCollection 2013.

Abstract

The cytochrome P450 (CYP) enzymes are major players in drug metabolism. More than 2,000 mutations have been described, and certain single nucleotide polymorphisms (SNPs) have been shown to have a large impact on CYP activity. Therefore, CYPs play an important role in inter-individual drug response and their genetic variability should be factored into personalized medicine. To identify the most relevant polymorphisms in human CYPs, a text mining approach was used. We investigated their frequencies in different ethnic groups, the number of drugs that are metabolized by each CYP, the impact of CYP SNPs, as well as CYP expression patterns in different tissues. The most important polymorphic CYPs were found to be 1A2, 2D6, 2C9 and 2C19. Thirty-four common allele variants in Caucasians led to altered enzyme activity. To compare the relevant Caucasian SNPs with those of other ethnicities a search in 1,000 individual genomes was undertaken. We found 199 non-synonymous SNPs with frequencies over one percent in the 1,000 genomes, many of them not described so far. With knowledge of frequent mutations and their impact on CYP activities, it may be possible to predict patient response to certain drugs, as well as adverse side effects. With improved availability of genotyping, our data may provide a resource for an understanding of the effects of specific SNPs in CYPs, enabling the selection of a more personalized treatment regimen.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Alleles*
  • Cytochrome P-450 Enzyme System* / biosynthesis
  • Cytochrome P-450 Enzyme System* / genetics
  • Gene Expression Regulation, Enzymologic*
  • Humans
  • Polymorphism, Single Nucleotide*
  • Precision Medicine*
  • White People

Substances

  • Cytochrome P-450 Enzyme System

Grants and funding

This work was supported by: BMBF ImmunoTox, European Union Seventh Framework Programme SYNSYS (Synaptic Systems: dissecting brain function in health and disease), DKTK. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.