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

Maria Savino, Davide Seripa, Antonietta P. Gallo, Maria Garrubba, Grazia D'Onofrio, Alessandra Bizzarro, Giulia Paroni, Francesco Paris, Patrizia Mecocci, Carlo Masullo, Alberto Pilotto, Stefano A. Santini

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)887-893
Number of pages7
JournalClinical Laboratory
Volume57
Issue number11-12
Publication statusPublished - 2011

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Cytochrome P-450 CYP2D6
Throughput
Pharmaceutical Preparations
Alleles
Polymorphism
Assays
Drug therapy
Gene Frequency

Keywords

  • CYP2D6
  • Cytochrome P4502D6
  • Genetic analysis
  • High-throughput analysis

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

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

In: Clinical Laboratory, Vol. 57, No. 11-12, 2011, p. 887-893.

Research output: Contribution to journalArticle

Savino, M, Seripa, D, Gallo, AP, Garrubba, M, D'Onofrio, G, Bizzarro, A, Paroni, G, Paris, F, Mecocci, P, Masullo, C, Pilotto, A & Santini, SA 2011, 'Effectiveness of a high-throughput genetic analysis in the identification of responders/non-responders to CYP2D6-metabolized drugs', Clinical Laboratory, vol. 57, no. 11-12, pp. 887-893.
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. / Effectiveness of a high-throughput genetic analysis in the identification of responders/non-responders to CYP2D6-metabolized drugs. In: Clinical Laboratory. 2011 ; Vol. 57, No. 11-12. pp. 887-893.
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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.",
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T1 - Effectiveness of a high-throughput genetic analysis in the identification of responders/non-responders to CYP2D6-metabolized drugs

AU - Savino, Maria

AU - Seripa, Davide

AU - Gallo, Antonietta P.

AU - Garrubba, Maria

AU - D'Onofrio, Grazia

AU - Bizzarro, Alessandra

AU - Paroni, Giulia

AU - Paris, Francesco

AU - Mecocci, Patrizia

AU - Masullo, Carlo

AU - Pilotto, Alberto

AU - Santini, Stefano A.

PY - 2011

Y1 - 2011

N2 - 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.

AB - 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.

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