Genetic Polymorphism of GSTP-1 Affects Cyclophosphamide Treatment of Autoimmune Diseases

Abstract

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.

Lactobacillus acidophilus LA85 ameliorates cyclophosphamide-induced immunosuppression by modulating Notch and TLR4/NF-κB signal pathways and remodeling the gut microbiota

“…Cyclophosphamide, as an immunosuppressant, is widely used in the treatment of various autoimmune diseases. 16 In addition, cyclophosphamide has an important role in antitumor and anticancer therapy, and its therapeutic effect is partly attributed to the stimulation of the body's immune response. 17 However, cyclophosphamide causes damage to the intestinal immune barrier and increases intestinal permeability, which in turn leads to gut microbiota disorders.…”

Influence of GSTP-1 Polymorphism on the Prognosis of Patients with High-Grade Glioma Who Received Temozolomide Plus Radiotherapy Adjuvant Treatment

“…The clinical outcome of this study was in line with that of our study to some extent in spite of the fact that they failed to perform the prognosis analysis. 31 And another retrospective study initiated by Yuan et al investigated the association of GSTP-1 and clinical outcome of gemcitabine-cisplatin chemotherapy in Chinese patients with NSCLC. 32 And the results suggested that A genotype carriers were significantly higher in sensitive group than in non-sensitive group, which was consistent with our study as well.…”

The Nitrogen Mustards

“…A retrospective study of 70 patients with proliferative lupus nephritis treated with cyclophosphamide showed that the 105 Ile/Val GSTP1 genotype was an independent predictor of poor renal outcome and that the GSTM1 null genotype was the only factor to affect the incidence of adverse effects (Audemard-Verger et al, 2016). Conversely, in a study of The Nitrogen Mustards 33 patients with a variety of autoimmune conditions treated with cyclophosphamide, those with the 105 Ile/Val GSTP1 variant had a higher response rate (Hajdin ak et al, 2020). In another study, the 105 Ile/Val GSTP1 and the 105 Val/Val GSTP1 genotypes increased the risk of short-term toxicity with pulsed high-dose cyclophosphamide in patients with SLE (Zhong et al, 2006).…”