Abstract
CYP2D6 is a key drug-metabolizing enzyme implicated in the biotransformation of approximately 25% of currently prescribed drugs. Interindividual and interethnic differences in CYP2D6 enzymatic activity, and hence variability in substrate drug efficacy and safety, are attributed to a highly polymorphic corresponding gene. This study aims at reviewing the frequencies of the most clinically relevant CYP2D6 alleles in the Arabs countries. Articles published before May 2021 that reported CYP2D6 genotype and allelic frequencies in the Arab populations of the Middle East and North Africa (MENA) region were retrieved from PubMed and Google Scholar databases. This review included 15 original articles encompassing 2737 individuals from 11 countries of the 22 members of the League of Arab States. Active CYP2D6 gene duplications reached the highest frequencies of 28.3% and 10.4% in Algeria and Saudi Arabia, respectively, and lowest in Egypt (2.41%) and Palestine (4.9%). Frequencies of the loss-of-function allele CYP2D6*4 ranged from 3.5% in Saudi Arabia to 18.8% in Egypt. The disparity in frequencies of the reduced-function CYP2D6*10 allele was perceptible, with the highest frequency reported in Jordan (14.8%) and the lowest in neighboring Palestine (2%), and in Algeria (0%). The reduced-function allele CYP2D6*41 was more prevalent in the Arabian Peninsula countries; Saudi Arabia (18.4%) and the United Arab Emirates (15.2%), in comparison with the Northern Arab-Levantine Syria (9.7%) and Algeria (8.3%). Our study demonstrates heterogeneity of CYP2D6 alleles among Arab populations. The incongruities of the frequencies of alleles in neighboring countries with similar demographic composition emphasize the necessity for harmonizing criteria of genotype assignment and conducting comprehensive studies on larger MENA Arab populations to determine their CYP2D6 allelic makeup and improve therapeutic outcomes of CYP2D6- metabolized drugs.
Highlights
Interindividual variability in drug response, affecting both drug efficacy and safety, is perceived as a major challenge in clinical practice
Studies were excluded if: they did not report the exact frequency of the concerned Cytochrome P450 2D6 (CYP2D6) alleles and only referred to them as mutant alleles, they were confined to CYP2D6 phenotypes regardless of genotypes, the genotyping approach is equivocal, or the genotyping details that support the resulting frequencies are not provided
Four studies were conducted in Egypt, two in Saudi Arabia, one study each in Iraq, Jordan, Lebanon, Morocco, Tunisia, and the The United Arab Emirates (UAE)
Summary
Interindividual variability in drug response, affecting both drug efficacy and safety, is perceived as a major challenge in clinical practice. CYPs content; it is involved in metabolizing approximately 25% of currently available drugs; such as tricyclic antidepressants, selective serotonin reuptake inhibitors, antipsychotics, opioids (e.g., codeine, and tramadol), antiarrhythmics, β-blockers, antineoplastic agents (e.g., tamoxifen and gefitinib), and a variety of other drugs [3, 4]. CYP2D6 is encoded by a highly polymorphic gene that has over 140 allelic variants characterized to date [5]. The CYP2D6 gene is located on the long arm of chromosome 22 (22q13.2) in a gene cluster that comprises two highly homologous pseudogenes, CYP2D7 and CYP2D8. It consists of nine exons and contains 4382 base pairs that code for a 497-amino acid protein [6]. There is a considerable number of alleles whose function is still unknown (e.g., *58, *73, *74, and *85), or uncertain (e.g., *22, *23, *37, and *43) [5, 7]
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