Characterization of the genetic profile of CYP2C19 in two South African populations.
OBJECTIVE
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.


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.


CONCLUSIONS
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.
Drögemöller
Britt I
BI
Department of Genetics, Stellenbosch University, Matieland, South Africa.
Wright
Galen E B
GE
Niehaus
Dana J H
DJ
Koen
Liezl
L
Malan
Stefanie
S
Da Silva
Danielle M
DM
Hillermann-Rebello
Renate
R
La Grange
Anthony M
AM
Venter
Mauritz
M
Warnich
Louise
L
D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D001483:Base Sequence; D044383:Black People / Q000235:genetics*; D045744:Cell Line, Tumor; D015331:Cohort Studies; D065731:Cytochrome P-450 CYP2C19; D017930:Genes, Reporter; D005838:Genotype; D006801:Humans; D008156:Luciferases / Q000235:genetics; D050216:Metabolic Detoxication, Phase I / Q000235:genetics; D008969:Molecular Sequence Data; D010597:Pharmacogenetics / Q000379:methods*; D010957:Plasmids; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D013019:South Africa; D014162:Transfection
D008156:Luciferases; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19