CYP2D6 belongs to the
cytochrome P450 superfamily of
enzymes and plays an important role in the metabolism of 20-25% of clinically used drugs including
antidepressants. It displays inter-individual and inter-ethnic variability in activity ranging from complete absence to excessive activity which causes
adverse drug reactions and toxicity or
therapy failure even at normal drug doses. This variability is due to genetic polymorphisms which form poor, intermediate, extensive or ultrarapid metaboliser phenotypes. This study aimed to determine
CYP2D6 alleles and their frequencies in the United Arab Emirates (UAE) local population.
CYP2D6 alleles and genotypes were determined by direct
DNA sequencing in 151 Emiratis with the majority being psychiatric patients on
antidepressants. Several new alleles have been identified and in total we identified seventeen alleles and 49 genotypes.
CYP2D6*1 (wild type) and
CYP2D6*2 alleles (extensive metaboliser phenotype) were found with frequencies of 39.1% and 12.2%, respectively.
CYP2D6*41 (intermediate metaboliser) occurred in 15.2%. Homozygous
CYP2D6*4 allele (poor metaboliser) was found with a frequency of 2% while homozygous and heterozygous
CYP2D6*4 occurred with a frequency of 9%.
CYP2D6*2xn, caused by gene duplication (ultrarapid metaboliser) had a frequency of 4.3%.
CYP2D6 gene duplication/multiduplication occurred in 16% but only 11.2% who carried more than 2 active functional alleles were considered ultrarapid metabolisers.
CYP2D6 gene deletion in one copy occurred in 7.5% of the study group. In conclusion,
CYP2D6 gene locus is heterogeneous in the UAE national population and no significant differences have been identified between the psychiatric patients and controls.