title: Effectiveness of a high-throughput genetic analysis in the identification of responders/non-responders to CYP2D6-metabolized drugs.
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.
authors.affiliation: Laboratory of Clinical Chemistry, Department of Clinical Pathology, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo (FG), Italy. mg.savino@operapadrepio.it
authors.forename: Maria
authors.initials: M
authors.lastname: Savino
authors.forename: Davide
authors.initials: D
authors.lastname: Seripa
authors.forename: Antonietta P
authors.initials: AP
authors.lastname: Gallo
authors.forename: Maria
authors.initials: M
authors.lastname: Garrubba
authors.forename: Grazia
authors.initials: G
authors.lastname: D'Onofrio
authors.forename: Alessandra
authors.initials: A
authors.lastname: Bizzarro
authors.forename: Giulia
authors.initials: G
authors.lastname: Paroni
authors.forename: Francesco
authors.initials: F
authors.lastname: Paris
authors.forename: Patrizia
authors.initials: P
authors.lastname: Mecocci
authors.forename: Carlo
authors.initials: C
authors.lastname: Masullo
authors.forename: Alberto
authors.initials: A
authors.lastname: Pilotto
authors.forename: Stefano A
authors.initials: SA
authors.lastname: Santini
mesh_terms: D000483:Alleles; D000544:Alzheimer Disease / Q000188:drug therapy / Q000235:genetics; D001711:Biotransformation / Q000235:genetics; D019389:Cytochrome P-450 CYP2D6 / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D000077265:Donepezil; D004351:Drug Resistance / Q000235:genetics; D017353:Gene Deletion; D020440:Gene Duplication; D005787:Gene Frequency; D005838:Genotype; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007189:Indans / Q000493:pharmacokinetics / Q000627:therapeutic use; D018697:Nootropic Agents / Q000493:pharmacokinetics / Q000627:therapeutic use; D010880:Piperidines / Q000493:pharmacokinetics / Q000627:therapeutic use; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D012494:Sampling Studies; D016037:Single-Blind Method
chemical_list: D007189:Indans; D018697:Nootropic Agents; D010880:Piperidines; D000077265:Donepezil; D019389:Cytochrome P-450 CYP2D6