ArticleBritish journal of clinical pharmacology2006
Relationship of glutathione S-transferase genotypes with side-effects of pulsed cyclophosphamide therapy in patients with systemic lupus erythematosus.
Article in British journal of clinical pharmacology, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 1 of them a synthesis that pooled it.
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Who cites it
38 citing papers in PubMed, 1 synthesis or guideline pooled it, 6 citations in OpenAlex.
- Influence of Genetic Variation of GST, CYP, and ABC on the Safety and Efficacy of Cyclophosphamide-Based Therapy.Clinical and translational science · 2025Pooled it
- Genetic markers in CYP2C19 and CYP2B6 for prediction of cyclophosphamide's 4-hydroxylation, efficacy and side effects in Chinese patients with systemic lupus erythematosus.British journal of clinical pharmacology · 2016Trial
- Gene polymorphisms in cyclophosphamide metabolism pathway,treatment-related toxicity, and disease-free survival in SWOG 8897 clinical trial for breast cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2010Trial
- GSTP1 Ile105Val polymorphism correlates with progression-free survival in MCRC patients treated with or without irinotecan: a study of the Dutch Colorectal Cancer Group.British journal of cancer · 2008Trial
- Prognostic role of glutathione S-transferase polymorphisms in acute myeloid leukemia.Leukemia · 2008Trial
- Genetic and epigenetic determinants of relapse risk in lupus nephritis.Lupus science & medicine · 2026Article
- Article
- A Novel Hybrid Peptide VLP-Aβ Efficiently Regulates Immunity by Stimulating Myeloid Differentiation Protein and Activating the NF-κB Pathway.International journal of molecular sciences · 2025Article
- Gene polymorphisms associated with immunosuppressant adverse effects in systemic lupus erythematosus: a narrative review.Frontiers in genetics · 2025Review
- Article
- Article
- GSTP1 rs4147581 C>G and NLRP3 rs3806265 T>C as Risk Factors for Chronic Obstructive Pulmonary Disease: A Case-Control Study.International journal of chronic obstructive pulmonary disease · 2024Article
- Article
- Extracellular Vesicles as Surrogates for Drug Metabolism and Clearance: Promise vs. Reality.Life (Basel, Switzerland) · 2023Review
- Uroprotective and Hepatoprotective Potential ofJournal of tropical medicine · 2022Article
- Pharmacogenomic associations of cyclophosphamide pharmacokinetic candidate genes with event-free survival in intermediate-risk rhabdomyosarcoma: A report from the Children's Oncology Group.Pediatric blood & cancer · 2021Article
- Glutathione S-transferase, catalase, and mitochondrial superoxide dismutase gene polymorphisms modulate redox potential in systemic lupus erythematosus patients from Manaus, Amazonas, Brazil.Clinical rheumatology · 2021Article
- GSTP1 rs1695 and rs1871042, and SOD2 rs4880 as molecular markers of lipid peroxidation in blood storage.Blood transfusion = Trasfusione del sangue · 2021Article
- Drug metabolising enzyme polymorphisms and chemotherapy-related ovarian failure in young breast cancer survivors.Journal of obstetrics and gynaecology : the journal of the Institute of Obstetrics and Gynaecology · 2021Article
- Konjac Glucomannan fromFood science & nutrition · 2021Article
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Authors and funding
9 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsCyclophosphamide (CTX) is an established treatment of severe systemic lupus erythematosus (SLE). Cytotoxic CTX metabolites are mainly detoxified by multiple glutathione S-transferases (GSTs). However, data are lacking on the relationship between the short-term side-effects of CTX therapy and GST genotypes. In the present study, the effects of common GSTM1, GSTT1, and GSTP1 genetic mutations on the severity of myelosuppression, gastrointestinal (GI) toxicity, and infection incidences induced by pulsed CTX therapy were evaluated in patients SLE.
methodsDNA was extracted from peripheral leucocytes in patients with confirmed SLE diagnosis (n = 102). GSTM1 and GSTT1 null mutations were analyzed by a polymerase chain reaction (PCR)-multiplex procedure, whereas the GSTP1 codon 105 polymorphism (Ile-->Val) was analyzed by a PCR-restriction fragment length polymorphism (RFLP) assay.
resultsOur study demonstrated that SLE patients carrying the genotypes with GSTP1 codon 105 mutation [GSTP1*-105I/V (heterozygote) and GSTP1*-105 V/V (homozygote)] had an increased risk of myelotoxicity when treated with pulsed high-dose CTX therapy (Odds ratio (OR) 5.00, 95% confidence interval (CI) 1.96, 12.76); especially in patients younger than 30 years (OR 7.50, 95% CI 2.14, 26.24), or in patients treated with a total CTX dose greater than 1.0 g (OR 12.88, 95% CI 3.16, 52.57). Similarly, patients with these genotypes (GSTP1*I/V and GSTP1*V/V) also had an increased risk of GI toxicity when treated with an initial pulsed high-dose CTX regimen (OR 3.33, 95% CI 1.03, 10.79). However, GSTM1 and GSTT1 null mutations did not significantly alter the risks of these short-term side-effects of pulsed high-dose CTX therapy in SLE patients.
conclusionsThe GSTP1 codon 105 polymorphism, but not GSTM1 or GSTT1 null mutations, significantly increased the risks of short-term side-effects of pulsed high-dose CTX therapy in SLE patients. Because of the lack of selective substrates for a GST enzyme phenotyping study, timely detection of this mutation on codon 105 may assist in optimizing pulsed high-dose CTX therapy in SLE patients.
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