Al Nasser Marzog S, Ahmad Mai A Alim A Sattar, Edris Sherif, Abdelfattah Ezz, Ali Ahmed S, Zaitoun Mohammad F, Alharbi Futoon H, Al Mahdi Hadiah B, Damanhouri Zoheir
Pharmaceutical Care Administration Armed Forces Hospital Southern Region, Khamis Mushayt, Saudi Arabia.
Department of Clinical Pharmacology, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia.
Saudi Pharm J. 2025 Aug 25;33(5):30. doi: 10.1007/s44446-025-00035-1.
Limited research has explored the genetic variability of CYP3A4 and CYP3A5 in the Saudi population, particularly concerning tacrolimus (Tac) therapy among Saudi kidney transplant patients (SKTP).
To investigate specific CYP3A4 and CYP3A5 polymorphisms in SKTP and evaluate their influence on Tac dose requirements and trough levels.
A total of 251 Saudi participants were recruited, comprising 129 kidney transplant patients and 122 healthy volunteers. Genomic DNA was extracted, and polymorphisms in CYP3A4 (*1B, *6, *18, *22) and CYP3A5 (*2, *3, *4) were analyzed using real-time PCR and allele-specific sequencing. Genotype frequencies and minor allele frequencies (MAF) were calculated, and the impact of CYP3A variants on Tac dosing and trough levels (C0) was assessed in SKTP.
The CYP3A41B polymorphism was absent, with all participants being homozygous wild type (G/G). For CYP3A5*3, 98.4% of participants carried the mutant genotype (*3/*3), while 1.6% carried the wild-type genotype (*1/*1). Patients with the wild-type allele (*1/*1) required significantly higher Tac doses and exhibited lower trough concentrations (C0) compared to those with the mutant genotype (3/3). Other polymorphisms, such as CYP3A422, were rare, with approximately 90% of participants carrying the wild-type allele.
This study highlights the high prevalence of the CYP3A5*3/*3 genotype and wild-type CYP3A4 alleles in the Saudi population. The genetic variability significantly affects Tac trough levels and dosing requirements necessary to achieve therapeutic targets. These findings underscore the importance of pharmacogeneticguided Tac dosing to optimize therapeutic outcomes in SKTP.
关于沙特人群中CYP3A4和CYP3A5的基因变异性，尤其是沙特肾移植患者（SKTP）中他克莫司（Tac）治疗方面的研究有限。
研究SKTP中特定的CYP3A4和CYP3A5多态性，并评估其对Tac剂量需求和血药谷浓度的影响。
共招募了251名沙特参与者，包括129名肾移植患者和122名健康志愿者。提取基因组DNA，使用实时PCR和等位基因特异性测序分析CYP3A4（*1B、*6、*18、*22）和CYP3A5（*2、*3、*4）的多态性。计算基因型频率和次要等位基因频率（MAF），并评估SKTP中CYP3A变异对Tac给药和血药谷浓度（C0）的影响。
未发现CYP3A41B多态性，所有参与者均为纯合野生型（G/G）。对于CYP3A53，98.4%的参与者携带突变基因型（*3/*3），而1.6%携带野生型基因型（*1/*1）。与携带突变基因型（*3/*3）的患者相比，携带野生型等位基因（*1/1）的患者需要显著更高的Tac剂量，且血药谷浓度（C0）较低。其他多态性，如CYP3A422，较为罕见，约90%的参与者携带野生型等位基因。
本研究突出了沙特人群中CYP3A5*3/*3基因型和野生型CYP3A4等位基因的高流行率。基因变异性显著影响Tac血药谷浓度和达到治疗目标所需的给药剂量。这些发现强调了药物遗传学指导下的Tac给药对优化SKTP治疗效果的重要性。
