title: Elucidation of CYP2D6 genetic diversity in a unique African population: implications for the future application of pharmacogenetics in the Xhosa population.
abstract: Genetic variation of the CYP2D6 gene has been associated with altered drug metabolism; however, limited studies have investigated CYP2D6 sequence diversity in African populations. We devised a CYP2D6 genotyping strategy to analyse the South African Xhosa population and genotype a Xhosa schizophrenia cohort, as CYP2D6 metabolises many antipsychotics and antidepressants. The entire CYP2D6 gene locus was sequenced in 15 Xhosa control individuals and the data generated were used to design a comprehensive genotyping strategy. Over 25 CYP2D6 alleles were genotyped in Xhosa controls and Xhosa schizophrenia patients using long-range PCR, DNA sequencing and single nucleotide primer extension analysis. Bioinformatic algorithms were used to predict the functional consequences of relevant mutations and samples were assigned CYP2D6 activity scores. A unique allele distribution was revealed and two rare novel alleles, CYP2D6*73 and CYP2D6*74, were identified. No significant differences in allele frequencies were detected between Xhosa controls and schizophrenia patients. This study provides i) comprehensive data on a poorly characterised population, ii) a valuable CYP2D6 genotyping strategy and iii) due to their unique genetic profile, provides the basis for pharmacogenetic intervention for Xhosa individuals.
authors.affiliation: Department of Genetics, Stellenbosch University, Private bag X1, Matieland 7602, South Africa.
authors.forename: Galen E B
authors.initials: GE
authors.lastname: Wright
authors.forename: Dana J H
authors.initials: DJ
authors.lastname: Niehaus
authors.forename: Britt I
authors.initials: BI
authors.lastname: Drögemöller
authors.forename: Liezl
authors.initials: L
authors.lastname: Koen
authors.forename: Andrea
authors.initials: A
authors.lastname: Gaedigk
authors.forename: Louise
authors.initials: L
authors.lastname: Warnich
mesh_terms: D044383:Black People / Q000235:genetics*; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic; D012559:Schizophrenia / Q000235:genetics*; D013019:South Africa
chemical_list: D019389:Cytochrome P-450 CYP2D6