Department of Applied Biotechnology and Food Science, Laboratory of Biochemistry and Molecular Biology, Budapest University of Technology and Economics, Szent Gellért tér 4., Budapest 1111, Hungary.
National Institute of Rheumatology and Physiotherapy, Clinical Immunology Adult and Pediatric Rheumatology, Frankel Leó u. 25-29., Budapest 1023, Hungary.
Molecules. 2020 Mar 28;25(7):1542. doi: 10.3390/molecules25071542.
Cyclophosphamide is one of the most potent and reliable anti-cancer and immunosuppressive drugs. In our study, 33 individuals with different autoimmune diseases were treated with cyclophosphamide according to standard protocols. The responses to the treatments were determined by measuring the alteration of several typical parameters characterizing the given autoimmune diseases over time. We concluded that about 45% of the patients responded to the treatment. Patients were genotyped for polymorphisms of the CYP3A4, CYP2B6, GSTM1, GSTT1, and GSTP1 genes and disease remission cases were compared to the individual polymorphic genotypes. It was found that the GSTP1 I105V allelic variation significantly associated with the cyclophosphamide treatment-dependent disease-remissions. At the same time the GSH content of the erythrocytes in the patients with I105V allelic variation did not change. It appears that the individuals carrying the Ile105Val SNP in at least one copy had a significantly higher response rate to the treatment. Since this variant of GSTP1 can be characterized by lower conjugation capacity that results in an elongated and higher therapeutic dose of cyclophosphamide, our data suggest that the decreased activity of this variant of GSTP1 can be in the background of the more effective disease treatment.
环磷酰胺是最有效和可靠的抗癌和免疫抑制剂之一。在我们的研究中，根据标准方案用环磷酰胺治疗了 33 名患有不同自身免疫性疾病的个体。通过测量随时间变化的几个典型参数来确定对治疗的反应，这些参数可用于描述给定的自身免疫性疾病。我们得出的结论是，大约 45%的患者对治疗有反应。对 CYP3A4、CYP2B6、GSTM1、GSTT1 和 GSTP1 基因的多态性进行了基因分型，并将疾病缓解病例与个体多态基因型进行了比较。发现 GSTP1 I105V 等位基因变异与环磷酰胺治疗依赖性疾病缓解显著相关。同时，I105V 等位基因变异患者的红细胞 GSH 含量没有变化。似乎至少携带一份 Ile105Val SNP 的个体对治疗的反应率显著更高。由于 GSTP1 的这种变体的结合能力较低，导致环磷酰胺的治疗剂量延长和升高，因此我们的数据表明，这种 GSTP1 变体的活性降低可能是疾病治疗更有效的背景。
