Mohammed Alkreathy Huda, Mohammed Eid Alsayyid Khlood, Alaama Jumana Y, Al Ghalayini Kamal, Karim Shahid, Esmat Ahmed, Damanhouri Zoheir A
Department of Pharmacology, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia.
Department of Medical Genetics, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia.
Saudi J Biol Sci. 2020 Oct;27(10):2727-2732. doi: 10.1016/j.sjbs.2020.06.022. Epub 2020 Jun 20.
Bisoprolol is an effective β1-adrenergic blocker, an inter-individual genetic variability was recorded in its response. This study aimed at investigating the association of CYP2D62A (rs1080985) and CYP2D610 (rs1065852) single-nucleotide polymorphism (SNP) with Bisoprolol response in cardiac patients attending King Abdulaziz University Hospital, Jeddah, Kingdom of Saudi Arabia.
In the study, 107 patients were enrolled. Five mL of venous blood was collected from each patient and genotyping for CYP2D62A and CYP2D610 using Vivid® CYP2D6 Green Screening Kit (Life Technologies, USA). Response to Bisoprolol was evaluated through assessment of diastolic and systolic blood pressure and by measuring Bisoprolol plasma level using triple quad mass spectrometer (TQ-MS).
All patients were found to carry homozygous wild type CYP2D610 (GG) and none were carrying heterozygous (GA) or mutant homozygous (AA) genotype. CYP2D62A allele was detected in the homozygous wild type (GG) in 70 out of 107 patients, the heterozygous (GC) in 19 patients, and the homozygous mutant (CC) in 18 patients with minor allele frequency (MAF) of 25.7%. The plasma concentrations of Bisoprolol in CC carriers were significantly lower than those in GG & CC carriers by 25%, and 51%; respectively. Higher systolic and diastolic blood pressures were also observed in CC carriers than GG and CC carriers.
There is a possible association of genotype with plasma concentration of bisoprolol. This could provide a helpful tool to choose the optimum dose for bisoprolol, depending on the patient's genotyping, in order to increase effectiveness and ameliorate its toxicity.
比索洛尔是一种有效的β1肾上腺素能阻滞剂，其反应存在个体间遗传变异性。本研究旨在调查沙特阿拉伯王国吉达阿卜杜勒阿齐兹国王大学医院的心脏病患者中CYP2D62A（rs1080985）和CYP2D610（rs1065852）单核苷酸多态性（SNP）与比索洛尔反应的相关性。
本研究纳入了107例患者。从每位患者采集5毫升静脉血，使用Vivid® CYP2D6绿色筛选试剂盒（美国赛默飞世尔科技公司）对CYP2D62A和CYP2D610进行基因分型。通过评估舒张压和收缩压以及使用三重四极杆质谱仪（TQ-MS）测量比索洛尔血浆水平来评估对比索洛尔的反应。
所有患者均携带纯合野生型CYP2D610（GG），无一例携带杂合子（GA）或突变纯合子（AA）基因型。在107例患者中，70例为纯合野生型（GG），19例为杂合子（GC），18例为纯合突变型（CC）检测到CYP2D62A等位基因，次要等位基因频率（MAF）为25.7%。CC携带者中比索洛尔的血浆浓度分别比GG和GC携带者低25%和51%。CC携带者的收缩压和舒张压也高于GG和GC携带者。
基因型与比索洛尔血浆浓度之间可能存在关联。这可以为根据患者的基因分型选择比索洛尔的最佳剂量提供一个有用的工具，以提高疗效并改善其毒性。
