Abstract
The cytochrome P450 CYP2D6 enzyme debrisoquine 4-hydroxylase metabolizes many different type of drugs commonly used in psychopharmacotherapy, such as tricyclic antidepressants and neuroleptics (1). The CYP2D6 gene, which encodes for the CYP2D6 enzyme, is part of a cluster on chromosome 22 that includes two to three related pseudogenes (2). Starting at the 5′ end of the cluster, there are two nonfunctional pseudogenes termed CYP2D8P and CYP2D7AP (an additional pseudogene, CYP2D7BP , also can be found) followed by the active gene CYP2D6 . Several mutated alleles of the CYP2D6 gene have been identified (3) and associated with alterations or polymorphisms in the metabolism of debrisoquine and related drugs metabolized by the CYP2D6 enzyme. As a result, CYP2D6 enzymatic activity ranges from ultrafast to a complete absence; the corresponding phenotypes are called ultrarapid (UM), extensive, and poor (PM) metabolizer. Unequal distribution of the alleles among different populations gives rise to interracial metabolic differences in addition to interindividual variation (4). Individuals homozygous or heterozygous for deficient CYP2D6 alleles metabolize drugs at a low rate, increasing the risks of side effects and drug toxicity. On the other hand, individuals with duplication/multiplication of the active CYP2D6 gene metabolize drugs at ultrarapid rate, hence requiring more than average doses of drugs to reach therapeutic plasma concentrations (5). The mechanism behind the duplication involves mainly the active allelic variant CYP2D62 (6). The occurrence of gene duplication varies widely, from 29% in Ethiopians (7), to 20% in Saudi Arabians (8), to 1–7% in Caucasians (9)(10), to 1–2% in Orientals (11)(12)(13), although not many data are available for the latter. Establishing the prevalence of duplicated CYP2D6 active alleles may help prevent therapeutic failure in UM individuals treated with CYP2D6 enzyme-substrates at standard doses. We investigated the prevalence of the …
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
