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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
Introduction of the AmpliChip CYP450 Test to a South African cohort: A platform comparative prospective cohort study
BMC Medical Genetics, Volume 14, No. 1, Article 20, Year 2013
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Description
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. © 2013 Dodgen et al.; licensee BioMed Central Ltd.
Available Materials
https://efashare.b-cdn.net/share/pmc/articles/PMC3605304/bin/1471-2350-14-20-S1.xlsx
https://efashare.b-cdn.net/share/pmc/articles/PMC3605304/bin/1471-2350-14-20-S2.xlsx
https://efashare.b-cdn.net/share/pmc/articles/PMC3605304/bin/1471-2350-14-20-S3.xls
https://efashare.b-cdn.net/share/pmc/articles/PMC3605304/bin/1471-2350-14-20-S4.xls
https://efashare.b-cdn.net/share/pmc/articles/PMC3605304/bin/1471-2350-14-20-S5.xlsx
https://efashare.b-cdn.net/share/pmc/articles/PMC3605304/bin/1471-2350-14-20-S6.pdf
Authors & Co-Authors
Dodgen, Tyren Mark
South Africa, Pretoria
University of Pretoria
Hochfeld, Warren E.
South Africa, Pretoria
University of Pretoria
Fickl, Heidi
South Africa, Pretoria
University of Pretoria
Asfaha, Sahle M.
South Africa, Pretoria
University of Pretoria
Durandt, Chrisna
South Africa, Pretoria
University of Pretoria
Rheeder, Paul
South Africa, Pretoria
University of Pretoria
Drögemöller, Britt I.
South Africa, Stellenbosch
Stellenbosch University
Wright, Galen E.B.
South Africa, Stellenbosch
Stellenbosch University
Warnich, Louise
South Africa, Stellenbosch
Stellenbosch University
Labuschagne, Christiaan De J.
South Africa, Pretoria
Inqaba Biotechnical Industries
Van Schalkwyk, Antoinette
South Africa, Pretoria
Inqaba Biotechnical Industries
Gaedigk, Andrea A.
United States, Kansas City
Children's Mercy Hospitals and Clinics
Pepper, Michael S.
South Africa, Pretoria
University of Pretoria
Switzerland, Geneva
Université de Genève
Statistics
Citations: 47
Authors: 13
Affiliations: 5
Identifiers
Doi:
10.1186/1471-2350-14-20
Research Areas
Genetics And Genomics
Study Design
Cross Sectional Study
Cohort Study
Study Approach
Quantitative