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.
