环磷酰胺治疗慢性淋巴细胞白血病患者CYP3A4和CYP3A5基因的药物遗传学研究

Heba M Elmaraghy, Menna Al-Adl, Eman R Saifeldein, Sahar M Elashmony, Magdy M Youssef, Afaf El-Said, Sherif Refaat, Abdallah E Mohammed
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引用次数: 0

摘要

背景:在临床环境中,大约75%的药物代谢归因于细胞色素P450酶。本研究旨在评估CYP3A4*1B和CYP3A5*3基因变异对慢性淋巴细胞白血病(CLL)患者环磷酰胺治疗后临床结果的影响。此外,我们旨在确定炎症状况对治疗反应的影响程度。方法:采用等位基因特异性扩增(ASA)-聚合酶链反应(PCR)检测150例埃及CLL患者CYP3A4*1B和CYP3A5*3多态性;同时检测血清白细胞介素6 (IL-6)和肿瘤坏死因子α (TNF-α)水平,以评估非遗传性炎症对CYP3A4和CYP3A5基因的影响。患者进一步接受化疗并随访。结果:CYP3A4*1B基因的等位基因频率为(74.3% vs. 25.7%), CYP3A5*3基因的等位基因频率为(73.4% vs. 26.6%)。携带CYP3A4*1B和CYP3A5*3基因或两种基因变体的患者比正常患者的应答率低(p < 0.001)。在非遗传性炎症效应方面,缓解组部分缓解患者的IL-6和TNF-α值高于完全缓解患者(p < 0.001),非缓解组病情进展的患者的IL-6和TNF-α值高于病情稳定患者(p < 0.001)。结论:CYP3A4*1B和CYP3A5*3变异可能是预测环磷酰胺化疗反应的有用指标。CYP3A4和CYP3A5的可变性应纳入个体化医疗,通过考虑影响反应的遗传和非遗传因素,尝试为个体患者优化药物剂量。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
CYP3A4 and CYP3A5 Genes in Cyclophosphamide-treated Chronic Lymphocytic Leukemia Patients: A Pharmacogenetics Study.

Background: Approximately 75% of drug metabolism in clinical settings is attributed to cytochrome P450 enzymes. This study aimed to assess the effects of the CYP3A4*1B and CYP3A5*3 genetic variations on the clinical results of individuals with chronic lymphocytic leukemia (CLL) following cyclophosphamide treatment. Furthermore, we aimed to ascertain how well the inflammatory condition affects the therapeutic response.

Methods: CYP3A4*1B and CYP3A5*3 polymorphisms were examined in 150 Egyptian CLL patients using allele-specific amplification (ASA)-polymerase chain reaction (PCR); serum interleukin 6 (IL-6) and tumor necrosis factor-alpha (TNF-α) levels were also measured to assess the non-genetic inflammatory effect on CYP3A4 and CYP3A5 genes. Patients further received chemotherapy and were subsequently followed up.

Results: The allelic frequencies of the CYP3A4*1B gene were (74.3% A-allele vs. 25.7% G-allele), and for CYP3A5*3, these frequencies were (73.4% A-allele vs. 26.6% G-allele). Patients with the CYP3A4*1B and CYP3A5*3 genes, or both variants, were less likely to respond than the normal patients (p < 0.001). Regarding the non-genetic inflammatory effect, patients in the response group who achieved partial remission were characterized by higher IL-6 and TNF-α values than those who achieved complete remission (p < 0.001), and patients in the non-response group who had a progressive disease were characterized by higher IL-6 and TNF-α values than those who had a stable disease (p < 0.001).

Conclusion: CYP3A4*1B and CYP3A5*3 variants could be helpful indicators in predicting the response to cyclophosphamide chemotherapy. CYP3A4 and CYP3A5 variability should be factored into personalized medicine, which attempts to optimize drug dosing for individual patients by considering genetic and non-genetic factors affecting the response.

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