Effectiveness of a high-throughput genetic analysis in the identification of responders/non-responders to CYP2D6-metabolized drugs

Clin Lab. 2011;57(11-12):887-93.

Abstract

Background: Recent studies investigating the single cytochrome P450 (CYP) 2D6 allele *2A reported an association with the response to drug treatments. More genetic data can be obtained, however, by high-throughput based-technologies. Aim of this study is the high-throughput analysis of the CYP2D6 polymorphisms to evaluate its effectiveness in the identification of patient responders/non-responders to CYP2D6-metabolized drugs.

Methods: An attempt to compare our results with those previously obtained with the standard analysis of CYP2D6 allele *2A was also made. Sixty blood samples from patients treated with CYP2D6-metabolized drugs previously genotyped for the allele CYP2D6*2A, were analyzed for the CYP2D6 polymorphisms with the AutoGenomics INFINITI CYP4502D6-I assay on the AutoGenomics INFINITI analyzer.

Results: A higher frequency of mutated alleles in responder than in non-responder patients (75.38 % vs 43.48 %; p = 0.015) was observed. Thus, the presence of a mutated allele of CYP2D6 was associated with a response to CYP2D6-metabolized drugs (OR = 4.044 (1.348 - 12.154). No difference was observed in the distribution of allele *2A (p = 0.320).

Conclusions: The high-throughput genetic analysis of the CYP2D6 polymorphisms better discriminate responders/non-responders with respect to the standard analysis of the CYP2D6 allele *2A. A high-throughput genetic assay of the CYP2D6 may be useful to identify patients with different clinical responses to CYP2D6-metabolized drugs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Alzheimer Disease / drug therapy
  • Alzheimer Disease / genetics
  • Biotransformation / genetics
  • Cytochrome P-450 CYP2D6 / deficiency
  • Cytochrome P-450 CYP2D6 / genetics*
  • Cytochrome P-450 CYP2D6 / metabolism
  • Donepezil
  • Drug Resistance / genetics
  • Gene Deletion
  • Gene Duplication
  • Gene Frequency
  • Genotype
  • High-Throughput Nucleotide Sequencing*
  • Humans
  • Indans / pharmacokinetics
  • Indans / therapeutic use
  • Nootropic Agents / pharmacokinetics
  • Nootropic Agents / therapeutic use
  • Piperidines / pharmacokinetics
  • Piperidines / therapeutic use
  • Polymorphism, Genetic*
  • Polymorphism, Single Nucleotide
  • Sampling Studies
  • Single-Blind Method

Substances

  • Indans
  • Nootropic Agents
  • Piperidines
  • Donepezil
  • Cytochrome P-450 CYP2D6