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

Abstract

Aims: This study was aimed at elucidating the common sequence variation present in the CYP2C19 gene within the South African Xhosa population and comparing it with the Cape Mixed Ancestry (CMA) population for possible future pharmacogenetic applications. Materials & methods: Common sequence variation was identified through the resequencing of 15 Xhosa individuals. The detected variants were prioritized for genotyping in an additional 85 Xhosa and 75 CMA individuals, while 5´-upstream variants were analyzed using dual luciferase reporter assays. Results: Resequencing of the Xhosa population revealed 30 variants, including the novel CYP2C19*27 and CYP2C19*28 alleles. CYP2C19*27, characterized by -1041G>A, caused a twofold decrease in luciferase activity, while CYP2C19*28 is characterized by the nonsynonymous V374I variant. In addition, the previously characterized variants, CYP2C19*2, CYP2C19*9 and CYP2C19*17, were present in both populations, while CYP2C19*3 was only observed in the CMA population. Conclusion: 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.

KEYWORDS::

• Cape Mixed Ancestry
• CYP2C19
• pharmacogenetics
• South Africa
• Xhosa

Acknowledgements

We would like to acknowledge the Xhosa individuals for their participation in this study, Ms M Bosman for technical assistance, the Central Analytical Facility of Stellenbosch University for assistance with sequence analyses and Dr O Ikediobi for critical reading of the manuscript.

Financial & competing interests disclosure

We would like to acknowledge the Harry Crossley Foundation and South African National Research Foundation for financial assistance. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Additional information

Funding

We would like to acknowledge the Harry Crossley Foundation and South African National Research Foundation for financial assistance. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.