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

• Published in: Clinical laboratory (Heidelberg) Vol. 57; no. 11-12; p. 887
• Main Authors: Savino, Maria, Seripa, Davide, Gallo, Antonietta P, Garrubba, Maria, D'Onofrio, Grazia, Bizzarro, Alessandra, Paroni, Giulia, Paris, Francesco, Mecocci, Patrizia, Masullo, Carlo, Pilotto, Alberto, Santini, Stefano A
• Format: Journal Article
• Language: English
• Published: Germany 2011
• Subjects: 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; 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
• ISSN: 1433-6510

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.
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.
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).
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.