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

dc.contributor.authorDodgen, Tyren M.
dc.contributor.authorHochfeld, Warren E.
dc.contributor.authorFickl, Heidi
dc.contributor.authorAsfaha, Sahle M.
dc.contributor.authorDurandt, Chrisna
dc.contributor.authorRheeder, Paul
dc.contributor.authorDrogemoller, Britt I.
dc.contributor.authorWright, Galen E. B.
dc.contributor.authorWarnich, Louise
dc.contributor.authorLabuschagne, Christiaan D. J.
dc.contributor.authorVan Schalkwyk, Antoinette
dc.contributor.authorGaedigk, Andrea
dc.contributor.authorPepper, Michael S.
dc.date.accessioned2013-06-26T13:59:53Z
dc.date.available2013-06-26T13:59:53Z
dc.date.issued2013-01
dc.date.updated2013-03-24T07:03:27Z
dc.descriptionThe original publication is available at http://www.biomedcentral.com/1471-2350/14/20en_ZA
dc.description.abstractAbstract 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 Test® (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_ZA
dc.description.versionPublishers' Versionen_ZA
dc.format.extent15 p. : ill.
dc.identifier.citationDodgen, T. M. et al. 2013. Introduction of the AmpliChip CYP450 Test to a South African cohort: a platform comparative prospective cohort study.BMC Medical Genetics, 14(1):20, doi:10.1186/1471-2350-14-20.en_ZA
dc.identifier.issn1471-2350 (online)
dc.identifier.otherdoi.org/10.1186/1471-2350-14-20
dc.identifier.urihttp://hdl.handle.net/10019.1/80949
dc.language.isoen_ZAen_ZA
dc.language.rfc3066en_ZA
dc.publisherBioMed Centralen_ZA
dc.rights.holderTyren M Dodgen et al.; licensee BioMed Central Ltd.en_ZA
dc.subjectPharmacogeneticsen_ZA
dc.subjectCytochrome P-450 enzymesen_ZA
dc.titleIntroduction of the AmpliChip CYP450 Test to a South African cohort : a platform comparative prospective cohort studyen_ZA
dc.typeArticleen_ZA
Files
Original bundle
Now showing 1 - 5 of 8
Loading...
Thumbnail Image
Name:
1471-2350-14-20.xml
Size:
235.69 KB
Format:
Extensible Markup Language
Description:
Loading...
Thumbnail Image
Name:
1471-2350-14-20.pdf
Size:
696.26 KB
Format:
Adobe Portable Document Format
Description:
Loading...
Thumbnail Image
Name:
1471-2350-14-20-S3.XLS
Size:
28 KB
Format:
Microsoft Excel
Description:
Loading...
Thumbnail Image
Name:
1471-2350-14-20-S1.XLSX
Size:
11.54 KB
Format:
Microsoft Excel XML
Description:
Loading...
Thumbnail Image
Name:
1471-2350-14-20-S6.PDF
Size:
49.87 KB
Format:
Adobe Portable Document Format
Description:
License bundle
Now showing 1 - 1 of 1
Loading...
Thumbnail Image
Name:
license.txt
Size:
1.95 KB
Format:
Item-specific license agreed upon to submission
Description: