Assessing the AmpliChip CYP450

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The Pharmacogenomics Journal (2009) 9, 34–41; doi:10.1038/tpj.2008.7; published online 1 July 2008

The AmpliChip CYP450 test: cytochrome P450 2D6 genotype assessment and phenotype prediction

M C Rebsamen¹, J Desmeules², Y Daali², A Chiappe¹, A Diemand¹, C Rey¹, J Chabert², P Dayer², D Hochstrasser¹ and M F Rossier¹

1. Service of Laboratory Medicine, University Hospitals, Geneva, Switzerland
2. Service of Clinical Pharmacology and Toxicology, University Hospitals, Geneva, Switzerland

Correspondence: Dr MC Rebsamen, Services of Laboratory Medicine, University Hospitals of Geneva, 24 Rue Micheli-du-Crest, 1211 Geneva 14, Switzerland. E-mail: michela.rebsamen@hcuge.ch

Received 14 December 2007; Revised 16 May 2008; Accepted 21 May 2008; Published online 1 July 2008.

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Abstract

Polymorphisms of the cytochrome P450 2D6 (CYP2D6) gene affecting enzyme activity are involved in interindividual variability in drug efficiency/toxicity. Four phenotypic groups are found in the general population: ultra rapid (UM), extensive (EM), intermediate (IM) and poor (PM) metabolizers. The AmpliChip CYP450 test is the first genotyping array allowing simultaneous analysis of 33 CYP2D6 alleles. The main aim of this study was to evaluate the performance of this test in CYP2D6 phenotype prediction. We first verified the AmpliChip CYP450 test genotyping accuracy for five CYP2D6 alleles routinely analysed in our laboratory (alleles 3,4,5,6, N; n=100). Results confirmed those obtained by real-time PCR. Major improvements using the array are the detection of CYP2D6 intermediate alleles and identification of the duplicated alleles. CYP2D6 phenotype was determined by assessing urinary elimination of dextromethorphan and its metabolite dextrorphan and compared to the array prediction (n=165). Although a low sensitivity of UM prediction by genotyping was observed, phenotype prediction was optimal for PM and satisfying for EM and IM.