Department of Pharmacology, Faculty of Medicine and Health Sciences, United Arab Emirates University, Al-Ain, United Arab Emirates.
PLoS One. 2011;6(12):e28943. doi: 10.1371/journal.pone.0028943. Epub 2011 Dec 22.
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. CYP2D61 (wild type) and CYP2D62 alleles (extensive metaboliser phenotype) were found with frequencies of 39.1% and 12.2%, respectively. CYP2D641 (intermediate metaboliser) occurred in 15.2%. Homozygous CYP2D64 allele (poor metaboliser) was found with a frequency of 2% while homozygous and heterozygous CYP2D64 occurred with a frequency of 9%. CYP2D62xn, 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.
CYP2D6 属于细胞色素 P450 超家族的酶，在 20-25%的临床使用药物的代谢中发挥重要作用，包括抗抑郁药。它在个体间和种族间的活性存在差异，从完全缺乏到过度活跃，这会导致不良反应和毒性或治疗失败，即使在正常药物剂量下也是如此。这种变异性是由于遗传多态性引起的，这些遗传多态性形成了不良、中间、广泛或超快代谢表型。本研究旨在确定阿拉伯联合酋长国（阿联酋）当地人群中的 CYP2D6 等位基因及其频率。通过直接 DNA 测序在 151 名阿联酋人（其中大多数是服用抗抑郁药的精神病人）中确定了 CYP2D6 等位基因和基因型。已经确定了几种新的等位基因，总共确定了 17 个等位基因和 49 种基因型。CYP2D61（野生型）和 CYP2D62 等位基因（广泛代谢表型）的频率分别为 39.1%和 12.2%。CYP2D641（中间代谢表型）的发生率为 15.2%。纯合 CYP2D64 等位基因（弱代谢表型）的频率为 2%，而纯合和杂合 CYP2D64 的频率为 9%。由基因重复（超快代谢表型）引起的 CYP2D62xn 的频率为 4.3%。CYP2D6 基因重复/多倍体发生在 16%，但只有 11.2%携带超过 2 个活性功能等位基因的人被认为是超快代谢者。研究组中发生了 7.5%的 CYP2D6 基因缺失。总之，CYP2D6 基因座在阿联酋国民群体中是异质的，精神病人和对照组之间没有发现显著差异。
