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

Dodgen, Tyren Mark; Hochfeld, Warren E.; Fickl, Heidi; Asfaha, Sahle; Durandt, Chrisna; Rheeder, Paul; Drögemöller, Britt I.; Wright, Galen E.B.; Warnich, Louise; Labuschagne, Christiaan; Schalkwyk, Antoinette van; Gaedigk, Andrea; Pepper, Michael Sean

doi:10.1186/1471-2350-14-20

Cited by 41 publications

(32 citation statements)

References 45 publications

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“…Of these, four were in Asian populations (two Chinese [Xiong et al, 2011, Chen et al, 2008]; two Korean [Park et al, 2008, Lee et al, 2006]) and eight involved Africans or African-Americans (Bains et al, 2013, Klein et al, 2005, Gaedigk and Coetsee, 2008, Leathart et al, 1998, Dickmann et al, 2001, Drögemöller et al, 2010, Wright et al, 2010, Dodgen et al, 2013). …”

Section: Resultsmentioning

confidence: 99%

African Genetic Diversity: Implications for Cytochrome P450-mediated Drug Metabolism and Drug Development

Rajman

Knapp²,

Morgan³

et al. 2017

EBioMedicine

102

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Genetic diversity is greater in Africa than in other continental populations. Genetic variability in genes encoding drug metabolizing enzymes may contribute to the high numbers of adverse drug reactions reported in Africa. We reviewed publications (1995–April 2016) reporting frequencies of known cytochrome P450 (CYP) variants in African populations. Using principal components analysis (PCA) we identified CYP alleles of potential clinical relevance with a marked difference in distribution in Africa, compared with Asian and Caucasian populations. These were CYP2B6*6, CYP2C8*2, CYP2D6*3, CYP2D6*17, CYP2D6*29, CYP3A5*6, and CYP3A5*7. We show clearly that there is greater diversity in CYP distribution in Africa than in other continental populations and identify a need for optimization of drug therapy and drug development there. Further pharmacogenetic studies are required to confirm the CYP distributions we identified using PCA, to discover uniquely African alleles and to identify populations at a potentially increased risk of drug-induced adverse events or drug inefficacy.

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Section: Resultsmentioning

confidence: 99%

African Genetic Diversity: Implications for Cytochrome P450-mediated Drug Metabolism and Drug Development

Rajman

Knapp²,

Morgan³

et al. 2017

EBioMedicine

102

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“…The novel allele identified was observed in a Black African individual, emphasising the importance of comprehensive genetic screening methods to accommodate low frequency alleles which may be of clinical relevance ( Matimba et al, 2009 ). Confidence in the genotyping assay used, including copy number discrepancies, was validated by Dodgen et al (2013) in which potential for bias or analytical error was addressed. As the sample size of each ethnic groups is small, allele frequencies will not be considered in this pilot cohort.…”

Section: Discussionmentioning

confidence: 99%

“…Genomic DNA (gDNA) was extracted from whole blood using the automated Maxwell® 16 system (Promega, Madison, WI, USA) according to instructions. Genotyping was performed using a CYP2D6 XL-PCR + Sequencing strategy as previously described ( Dodgen et al, 2013 ). Briefly, the strategy makes use of two duplex long-range PCR (polymerase chain reaction) assays, one for CYP2D6 * 5 (complete gene deletion) and the other for duplication detection followed by CYP2D6 gene sequencing for allele determination.…”

Section: Methodsmentioning

confidence: 99%

“…An adjusted version of the Activity Score (AS) system ( Gaedigk et al, 2008 ) was used to predict CYP2D6 phenotype. The adjusted phenotype prediction system was adopted from genotype–phenotype comparisons described by Dodgen et al (2013) , where activity is Increased = 2.0, Normal = 1.0, Decreased = 0.5 and None = 0.0 using information from the Human Cytochrome P450 ( CYP ) Allele Nomenclature Committee's online database for CYP2D6 . CYP2D6 * 17 , traditionally assigned an AS of 0.5, was given a score of 1.0, as this allele has been found to metabolise risperidone with full function ( de Leon et al, 2009 ).…”

Section: Methodsmentioning

confidence: 99%

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Risperidone-associated adverse drug reactions and CYP2D6 polymorphisms in a South African cohort

Dodgen

Eloff

Mataboge

et al. 2015

Applied & Translational Genomics

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BackgroundContradictory information exists regarding the influence of CYP2D6 polymorphisms on adverse drug reactions (ADRs) (extrapyramidal symptoms (EPS) and weight gain) related to risperidone treatment. This prompted us to evaluate the influence of CYP2D6 genetic variation in a cohort of South African patients who presented with marked movement disorders and/or weight gain while on risperidone treatment.MethodsPatients who were experiencing marked risperidone ADRs were recruited from Weskoppies Public Psychiatric Hospital. As poor or intermediate metabolism was expected, comprehensive CYP2D6 sequence variations were evaluated using XL-PCR + Sequencing.ResultsNo statistically significant association was found between CYP2D6 poor metabolism and risperidone ADRs. An inverse relationship between EPS and weight gain was however identified. A novel CYP2D6 allele was identified which is unlikely to affect metabolism based on in silico evaluation.ConclusionCYP2D6 variation appeared not to be a good pharmacogenetic marker for predicting risperidone-related ADRs in this naturalistic South African cohort. Evaluation of a larger cohort would be needed to confirm these observations, including an examination of the role of potential intermediaries between the hypothesised genetic and clinical phenotypes.

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“…Amplicons were hybridized and genotyping was performed using a kit from Saileqi BIOTECH (Zhuhai, Guangdong, China). 31 Patients with no LOF allele were defined as extensive metabolizers (EM); those with one LOF allele, as intermediate metabolizers (IM); and those with both LOF alleles, as poor metabolizers (PMs).…”

Section: Genetic Analysismentioning

confidence: 99%

<p>Impacts of <em>CYP2C19</em> Polymorphism and Clopidogrel Dosing on in-Stent Restenosis: A Retrospective Cohort Study in Chinese Patients</p>

Zhang

Wang

Zhang

et al. 2020

DDDT

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Objective: This retrospective cohort study is to analyze the impacts of CYP2C19 polymorphism and clopidogrel dosing on in-stent restenosis (ISR) after coronary stenting. Methods: Totally, 111 patients were included, who underwent percutaneous coronary intervention (PCI) with drug-eluting stent. Patients received clopidogrel treatment after the intervention on the background treatment with aspirin, based on the genotypes: 75 mg clopidogrel once each day for subjects without CYP2C19 loss-of-function (LOF) alleles (n=51; EM), 75 mg clopidogrel once each day (n=27; IM75) or twice each day (n=33; IM150) for subjects with one CYP2C19 LOF allele. ISR at 3-18 months after coronary stenting was assessed. Results: ISR rate was significantly higher in the IM75 group (40.7%) than the EM group (11.8%). ISR rate in the IM150 group was lower than the IM75 group (6.1% vs 40.7%), and comparable to that in the EM group. Multivariate logistic regression showed that both CYP2C19 genotype and clopidogrel dosing were associated with the risk of ISR after adjusting the relevant confounding factors. ISR risk was higher in the IM patients than the EM patients. Patients with clopidogrel dose of 75 mg once each day had significantly higher risk of ISR than those with the dose of 75 mg twice each day. Conclusion: Increased dose of clopidogrel may reduce the risk of ISR after PCI in CYP2C19 LOF allele(s) carriers. The presence of CYP2C19 LOF allele(s) increases the risk of ISR after stenting, which could be counteracted by the increased dose of clopidogrel.

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

Cited by 41 publications

References 45 publications

African Genetic Diversity: Implications for Cytochrome P450-mediated Drug Metabolism and Drug Development

African Genetic Diversity: Implications for Cytochrome P450-mediated Drug Metabolism and Drug Development

Risperidone-associated adverse drug reactions and CYP2D6 polymorphisms in a South African cohort

<p>Impacts of <em>CYP2C19</em> Polymorphism and Clopidogrel Dosing on in-Stent Restenosis: A Retrospective Cohort Study in Chinese Patients</p>

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