Department of Oncology, Albairouni University Hospital, Faculty of Medicine, Damascus University, Damascus, Syrian Arab Republic.
Program of Clinical and Hospital Pharmacy, Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Damascus University, Mezzeh Autostrad, Damascus, Syrian Arab Republic.
Hum Genomics. 2022 Feb 5;16(1):6. doi: 10.1186/s40246-022-00378-z.
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 CYP2D64 ranged from 3.5% in Saudi Arabia to 18.8% in Egypt. The disparity in frequencies of the reduced-function CYP2D610 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.
CYP2D6 是一种关键的药物代谢酶，参与大约 25%的目前处方药物的生物转化。CYP2D6 酶活性的个体间和种族间差异，以及底物药物疗效和安全性的变异性，归因于高度多态性的相应基因。本研究旨在综述阿拉伯国家中最具临床意义的 CYP2D6 等位基因的频率。从 PubMed 和 Google Scholar 数据库中检索到 2021 年 5 月之前发表的报告中东和北非（MENA）地区阿拉伯人群 CYP2D6 基因型和等位基因频率的文章。本综述包括 15 篇原始文章，涵盖了来自阿拉伯国家联盟 22 个成员国中的 11 个国家的 2737 个人。在阿尔及利亚和沙特阿拉伯，活性 CYP2D6 基因重复的频率分别达到了 28.3%和 10.4%的最高频率，而在埃及（2.41%）和巴勒斯坦（4.9%）则最低。失活等位基因 CYP2D64 的频率范围从沙特阿拉伯的 3.5%到埃及的 18.8%。功能降低的 CYP2D610 等位基因的频率差异明显，报道的最高频率在约旦（14.8%），最低在邻国巴勒斯坦（2%），在阿尔及利亚（0%）。功能降低的 CYP2D6*41 等位基因在阿拉伯半岛国家更为普遍；沙特阿拉伯（18.4%）和阿拉伯联合酋长国（15.2%），与北部阿拉伯-黎凡特的叙利亚（9.7%）和阿尔及利亚（8.3%）相比。我们的研究表明阿拉伯人群中 CYP2D6 等位基因存在异质性。具有相似人口结构的邻国之间等位基因频率的不一致性强调了需要协调基因型分配标准，并对更大的 MENA 阿拉伯人群进行综合研究，以确定他们的 CYP2D6 等位基因组成，改善 CYP2D6 代谢药物的治疗效果。
