Dataset Information

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.

SUBMITTER: Hajdinak P

PROVIDER: S-EPMC7180851 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Hajdinák Péter P Szabó Melinda M Kiss Emese E Veress Lili L Wunderlich Lívius L Szarka András A

Molecules (Basel, Switzerland) 20200328 7

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 polymorph ...[more]

PMID: 32231024

Similar Datasets

Project description:BackgroundGlutathione S-Transferase P 1 (GSTP-1) gene plays an important physiological role in the body. The present study was conducted to identify the clinical implication of GSTP-1 gene polymorphism on the prognosis of patients with high-grade glioma (HGG) who received temozolomide plus radiotherapy adjuvant treatment.MethodsThis study recruited a total of 186 patients with HGG who were treated with temozolomide plus radiotherapy adjuvant regimen (retrospectively). Baseline clinical characteristics were obtained and the prognostic data of the patients were collected. Peripheral blood specimen of patients was preserved for genotyping of GSTP-1 polymorphism during hospitalization. Correlation analysis was carried out accordingly. Additionally, fresh peripheral blood specimens that were available for mRNA expression analysis were collected for the mRNA expression analysis.ResultsThe median progression-free survival (PFS) and overall survival (OS) of the 186 patients with HGG who received temozolomide plus radiotherapy regimen was 8.5 months (95% CI: 5.95-11.05) and 15.5 months (95% CI: 11.49-19.51), respectively. The prevalence of 313A>G among 186 patients with glioma was AA genotype: 126 cases (67.7%), AG genotype: 54 cases (29.1%), GG genotype: 6 cases (3.2%), minor allele frequency of 313A>G was 0.18. Association analysis suggested that the median PFS of patients with AA and AG/GG genotypes was 11.2 and 5.0 months, respectively (χ2=11.17, P=0.001). Furthermore, the median OS of patients with AA and AG/GG genotypes was 18.9 and 10.5 months, respectively (χ2=12.684, P<0.001). Besides, when adjusted for PFS in multivariate Cox regression analysis, AG/GG genotype was an independent factor for PFS (HR=0.48, P=0.006). The mRNA expression results indicated that mRNA expression of GSTP-1 in patients with AG/GG genotypes of 313A>G was significantly higher than that of patients with AA genotype (P<0.001).ConclusionGSTP-1 polymorphism 313A>G might be used as a potential biomarker to predict the prognosis of patients with HGG who received temozolomide plus radiotherapy adjuvant treatment.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets