CYP2D6 polymorphisms in selected South African populations

English: Debrisoquine 4-hydroxylase, also known as CYP206, is a cytochrome P450 enzyme responsible for the metabolism of many commonly used drugs such as antispychotics, beta-blockers, opiates and tricyclic antidepressants. Polymorphic expression of CYP206 is observed in the interethnic and inter-individual variability in patients undergoing treatment with these drugs. Two distinct phenotypes have been described for this enzyme in Caucasian populations, namely extensive and poor metabolisers. The poor metaboliser phenotype behaves as an autosomal recessive trait occurring in about 7% of Caucasians. Major discordance has been observed when comparing Caucasian data with data from other ethnic groups. Accurate prediction of a patient's genotype could be important for many cl inically used drugs as poor metabolisers are at a high risk for adverse drug reactions, onset of toxicity and even therapeutic failure. Early or preventative therapy guided by genotyping could significantly enhance the clinical outcome for these patients. In this study we determined the frequency of CYP206 polymorphisms in three Southern African populations, namely Caucasian (control), Black and Coloureds. Our results for the Caucasian group largely confirm the findings of other studies in the sense that 96 % of subjects are extensive metabolisers (normal). However, based on their genotypes, only 67 % of Coloured and 69 % of Black subjects are predicted to be extensive metabolisers. A high prevalence of intermediate (IM) metabolisers was observed for both the Black (24 %) and Coloured (26 %) groups. CYP206*17 occurred at a high frequency in the Black (0.2324) and Coloured (0.1301) goups, while CYP206*10 also occurred at a high frequency in the Coloured (0.1301) group. Both these groups show reduced-activity alleles unique to them, not found in the Caucasian subjects. If confirmed by phenotyping subjects on a relevant treatment, these findings may have implications for treatment of patients with drugs metabolised by CYP206.