Introduction of the AmpliChip CYP450 test to a South African cohort : a platform comparative prospective cohort study

Show simple item record Dodgen, Tyren Mark Hochfeld, Warren Ernst Fickl, Heidi Asfaha, Sahle M. Durandt, Chrisna Rheeder, Paul Drögemoller, Britt I. Wright, Galen E.B. Warnich, Louise Labuschagne, Christiaan D.J. Van Schalkwyk, Antoinette Gaedigk, Andrea Pepper, Michael Sean 2013-06-26T06:21:25Z 2013-06-26T06:21:25Z 2013-01-29
dc.description.abstract BACKGROUND: Adverse drug reactions and lack of therapeutic efficacy associated with currently prescribed pharmacotherapeutics may be attributed, in part, to inter-individual variability in drug metabolism. Studies on the pharmacogenetics of Cytochrome P450 (CYP) enzymes offer insight into this variability. The objective of this study was to compare the AmpliChip CYP450 TestW (AmpliChip) to alternative genotyping platforms for phenotype prediction of CYP2C19 and CYP2D6 in a representative cohort of the South African population. METHODS: AmpliChip was used to screen for thirty-three CYP2D6 and three CYP2C19 alleles in two different cohorts. As a comparison cohort 2 was then genotyped using a CYP2D6 specific long range PCR with sequencing (CYP2D6 XL-PCR + Sequencing) platform and a PCR-RFLP platform for seven CYP2C19 alleles. RESULTS: Even though there was a low success rate for the AmpliChip, allele frequencies for both CYP2D6 and CYP2C19 were very similar between the two different cohorts. The CYP2D6 XL-PCR + Sequencing platform detected CYP2D6*5 more reliably and could correctly distinguish between CYP2D6*2 and *41 in the Black African individuals. Alleles not covered by the AmpliChip were identified and four novel CYP2D6 alleles were also detected. CYP2C19 PCR-RFLP identified CYP2C19*9,*15, *17 and *27 in the Black African individuals, with *2, *17 and *27 being relatively frequent in the cohort. Eliminating mismatches and identifying additional alleles will contribute to improving phenotype prediction for both enzymes. Phenotype prediction differed between platforms for both genes. CONCLUSION: Comprehensive genotyping of CYP2D6 and CYP2C19 with the platforms used in this study, would be more appropriate than AmpliChip for phenotypic prediction in the South African population. Pharmacogenetically important novel alleles may remain undiscovered when using assays that are designed according to Caucasian specific variation, unless alternate strategies are utilised. en_US
dc.description.librarian am2013 en_US
dc.description.sponsorship This work was supported financially by the Departments of Pharmacology and Immunology, University of Pretoria; the National Research Foundation of South Africa (NRF); the National Health Laboratory Services of South Africa (NHLS); the Medical Research Council (MRC) and Ampath Laboratories, South Africa. en_US
dc.description.uri en_US
dc.identifier.citation Dodgen et al.: Introduction of the AmpliChip CYP450 Test to a South African cohort: a platform comparative prospective cohort study. BMC Medical Genetics 2013 14:20. en_US
dc.identifier.issn 1471-2350
dc.identifier.other 10.1186/1471-2350-14-20
dc.language.iso en en_US
dc.publisher BioMed Central en_US
dc.rights © 2013 Dodgen et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. en_US
dc.subject AmpliChip CYP450 Test en_US
dc.subject South African cohort en_US
dc.title Introduction of the AmpliChip CYP450 test to a South African cohort : a platform comparative prospective cohort study en_US
dc.type Article en_US

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