Characterization of the Genetic Profile of
            <i>CYP2C19</i>
            in Two South African Populations

Drögemöller, Britt I.; Wright, Galen E.B.; Niehaus, Dana J.H.; Koen, Liezl; Malan, Stefanie; Silva, Danielle M Da; Hillermann, Renate; Venter, Mauritz; Warnich, Louise

doi:10.2217/pgs.10.90

Cited by 46 publications

(47 citation statements)

References 41 publications

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“…Of the three IM associated alleles, CYP2C19*9 and CYP2C19*27 have only been reported in five African countries. The recently reported UM associated allele, CYP2C19*17, has been investigated in three African populations and is present at frequencies of 10-17% [55][56][57], which is consistent with that seen in Caucasian populations, but is far higher than the <1% in Asians [54].…”

Section: Cyp2c19 Cyp2d6 and The Management Of Major Depressive Disorsupporting

confidence: 74%

Priority pharmacogenetics for the African continent: focus on CYP450

Alessandrini

Pepper

2014

Pharmacogenomics

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SummaryCountries in Africa have a high burden of communicable disease, and are experiencing an increase in non-communicable diseases due to the effects of globalization, industrialization and urbanization.The costs incurred through adverse drug reactions and non-responsiveness to therapy further aggravate the situation, and the application of pharmacogenetic principles is likely to provide some relief. Having undertaken an extensive evaluation of CYP450 reports in Africa, our objective was to map out areas of need based on regional disease burdens. The data confirms a paucity of CYP450 reports and illustrates large regions for which no population information exists. There is a dire need to address the health problems of Africa, and wide-scale pharmacogenetic profiling of these populations will add significantly to improving patient care on the continent. Priority pharmacogenetics for the African continent gives precedence to the profiling of clinically relevant pharmacogenetic biomarkers, and defines the immediate need in the context of disease burden.

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Section: Cyp2c19 Cyp2d6 and The Management Of Major Depressive Disorsupporting

confidence: 74%

Priority pharmacogenetics for the African continent: focus on CYP450

Alessandrini

Pepper

2014

Pharmacogenomics

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“…The absence of CYP2C19*10 and an alternative linkage disequilibrium pattern found for CYP2C19*17, emphasised the differences in genetic composition between African-Americans and the Xhosa from South Africa. This, along with allelic frequency differences between the Venda, Xhosa and Cape Coloureds, reiterates the importance of acknowledging diversity within Africa and those of the African diaspora [19]. More comprehensive African-specific genotyping strategies should therefore be considered when evaluating pharmacogenetic variation in South Africans.…”

Section: Introductionmentioning

confidence: 89%

“…CYP2C19 was evaluated using PCR-RFLP analysis as described previously [19], which entailed the amplification of eight exonic regions and enzymatic digestion to identify the allele-defining …”

Section: Cyp2c19 Genotypingmentioning

confidence: 99%

“…From these studies, a number of interesting observations can be made. The predominantly Asian allele, CYP2C19*3, was only detected in the Cape Coloured population, reflecting the high level of admixture [19]. The absence of CYP2C19*10 and an alternative linkage disequilibrium pattern found for CYP2C19*17, emphasised the differences in genetic composition between African-Americans and the Xhosa from South Africa.…”

Section: Introductionmentioning

confidence: 95%

“…3 Genetic variation in CYP2C19 (OMIM 124020) has been associated with variable responses to numerous drugs including clopidogrel (anticoagulant), citalopram (and many other antidepressants), proguanil (prophylactic anti-malarial) and omeprazole (and other proton pump inhibitors) [6][7][8][9][10][11][12] The non-functional CYP2C19*2 and *3 alleles are the most commonly genotyped and have been prioritised in many CYP2C19 studies [13]. Responsible for increased CYP2C19 expression, CYP2C19*17 is important for the prediction of UMs and has been found to be relatively frequent in certain populations [14][15][16][17][18][19]. The above-mentioned alleles have been prioritised based on observations in cohorts of predominantly European and Asian descent.…”

Section: Introductionmentioning

confidence: 99%

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Evaluation of Predictive Cyp2C19 Genotyping Assays Relative to Measured Phenotype in a South African Cohort

et al. 2015

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Aim: To align predicted and measured CYP2C19 phenotype in a South African cohort. Materials and methods:Genotyping of CYP2C19*2, *3, *9, *15, *17, *27 and *28 was performed using PCR-RFLP, and an Activity Score (AS) system was used to predict phenotype. 2True phenotype was measured using plasma concentrations of omeprazole and its metabolite 5'-hydroxyomperazole. Results: Partial genotype-phenotype discrepancies were reported, and an adapted AS system was developed, which showed a marked improvement in phenotype prediction. Results highlight the need for a more comprehensive CYP2C19 genotyping approach to improve prediction of omeprazole metabolism. Conclusion: Evidence for the utility of a CYP2C19 AS system is provided, for which the accuracy can be further improved by means of comprehensive genotyping and substrate specific modification.

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Metabolism of testosterone and progesterone by cytochrome P450 2C19 allelic variants

Takeji,

Okada,

Hayashi

et al. 2023

Biopharm & Drug Disp

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CYP2C19 is a member of the human microsomal cytochrome P450 (CYP). Significant variation in CYP2C19 levels and activity can be attributed to polymorphisms in this gene. Wildtype CYP2C19 and 13 mutants (CYP2C19.1B, CYP2C19.5A, CYP2C19.5B, CYP2C19.6, CYP2C19.8, CYP2C19.9, CYP2C19.10, CYP2C19.11, CYP2C19.13, CYP2C19.16, CYP2C19.19, CYP2C19.23, CYP2C19.30, and CYP2C19.33) were coexpressed with NADPH‐cytochrome P450 reductase in Escherichia coli. Hydroxylase activity toward testosterone and progesterone was also examined. Ten CYP2C19 variants showed Soret peaks (450 nm) typical of P450 in the reduced CO‐difference spectra. CYP2C19.11 and CYP2C19.23 showed higher testosterone 11α, 16α‐/17‐ and progesterone 6β‐,21‐,16α‐/17α‐hydroxylase activities than CYP2C19.1B. CYP2C19.6, CYP2C19.16, CYP2C19.19, and CYP2C19.30 showed lower activity than CYP2C19.1B. CYP2C19.9, CYP2C19.10. CYP2C19.13, and CYP2C19.33 showed different hydroxylation activities than CYP2C19.1B. These results indicated that CYP2C19 variants have very different substrate specificities for testosterone and progesterone.

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Characterization of the Genetic Profile of CYP2C19 in Two South African Populations

Abstract: Our data demonstrate that both the Xhosa and CMA populations exhibit unique genetic profiles that could influence the outcome of drug therapy in these populations.

Cited by 46 publications

References 41 publications

Priority pharmacogenetics for the African continent: focus on CYP450

Priority pharmacogenetics for the African continent: focus on CYP450

Evaluation of Predictive Cyp2C19 Genotyping Assays Relative to Measured Phenotype in a South African Cohort

Metabolism of testosterone and progesterone by cytochrome P450 2C19 allelic variants

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