title: Characterization of the genetic profile of CYP2C19 in two South African populations.
abstract: 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.
authors: Department of Genetics, Stellenbosch University, Matieland, South Africa.
authors: Britt I
authors: BI
authors: Drögemöller
authors: Galen E B
authors: GE
authors: Wright
authors: Dana J H
authors: DJ
authors: Niehaus
authors: Liezl
authors: L
authors: Koen
authors: Stefanie
authors: S
authors: Malan
authors: Danielle M
authors: DM
authors: Da Silva
authors: Renate
authors: R
authors: Hillermann-Rebello
authors: Anthony M
authors: AM
authors: La Grange
authors: Mauritz
authors: M
authors: Venter
authors: Louise
authors: L
authors: Warnich
mesh_terms: 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
chemical_list: D008156:Luciferases; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19