Elucidation of CYP2D6 Genetic Diversity in a Unique African Population: Implications for the Future Application of Pharmacogenetics in the Xhosa Population

作者：Wright Galen E B; Niehaus Dana J H; Droegemoeller Britt I; Koen Liezl; Gaedigk Andrea; Warnich Louise^*

来源：Annals of Human Genetics, 2010, 74: 340-350.

DOI：10.1111/j.1469-1809.2010.00585.x

• CYP2D6
• pharmacogenetics
• schizophrenia
• South African population
• Xhosa

P>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.

• 出版日期2010-7