Department of Pharmacology and Therapeutics, College of Medicine, University of AL-Qadisiyah, Iraq.
Department of Pharmacology and Therapeutics, College of Pharmacy, University of AL-Qadisiyah, Iraq.
Gene. 2019 Jun 30;703:112-119. doi: 10.1016/j.gene.2019.04.012. Epub 2019 Apr 6.
This study aims to investigate the different clinically relevant allele variants (allele frequencies) of CYP2D6 gene and to determine whether a specific genotype of CYP2D6 gene (based on genetic polymorphism "allelic types" and combination) have impact on metoprolol effectiveness (clinical outcome) in patients who have acute coronary syndrome (ACS). The study included 250 patients with ACS who were classified into 2 study groups, 125 patients received metoprolol and served as a study group (Group1) and 125 who received no metoprolol therapy (due to contraindication to the medication) and served as a control group (Group 2). Venous blood samples were taken from all participants for DNA extraction. Urine samples were also collected to assess the metabolic ratio using High-performance liquid chromatography (HPLC) technique. There was significant variation in the distribution of Iraqi patients with respect to CYP2D6 allelic polymorphism as compared to similar patients in other countries. Besides, this significant difference existed in patients' outcome in terms of morbidity and mortality in respect to variable genotypes and phenotypes. We recommend a dose individualization of metoprolol in patients with ACS is essential to improve patients' outcome.
本研究旨在探讨 CYP2D6 基因的不同临床相关等位变异体（等位基因频率），并确定 CYP2D6 基因的特定基因型（基于遗传多态性“等位类型”和组合）是否对急性冠状动脉综合征（ACS）患者的美托洛尔疗效（临床结局）有影响。该研究纳入了 250 名 ACS 患者，将其分为 2 个研究组，其中 125 名患者接受美托洛尔治疗，作为研究组（组 1），125 名因药物禁忌而未接受美托洛尔治疗的患者作为对照组（组 2）。所有参与者均采集静脉血样进行 DNA 提取。还收集了尿液样本，使用高效液相色谱（HPLC）技术评估代谢比值。与其他国家的类似患者相比，伊拉克患者在 CYP2D6 等位基因多态性的分布方面存在显著差异。此外，在不同基因型和表型方面，患者的发病率和死亡率方面的预后存在显著差异。我们建议对 ACS 患者进行美托洛尔剂量个体化，以改善患者的预后。
