ArticleClinical rheumatology2021
Influence of glutathione S transferase A1 gene polymorphism (-69C > T, rs3957356) on intravenous cyclophosphamide efficacy and side effects: a case-control study in Egyptian patients with lupus nephritis.
Article in Clinical rheumatology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.
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Who cites it
10 citing papers in PubMed, 1 synthesis or guideline pooled it, 17 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
- Article
- Cyclophosphamide Pharmacogenomic Variation in Cancer Treatment and Its Effect on Bioactivation and Pharmacokinetics.Advances in pharmacological and pharmaceutical sciences · 2024Review
- Condensed Fuzheng extract increases immune function in mice with cyclophosphamide-induced immunosuppression.Food science & nutrition · 2022Article
- Influence of Glutathione-S-Transferase A1*B Allele on the Metabolism of the Aromatase Inhibitor, Exemestane, in Human Liver Cytosols and in Patients Treated With Exemestane.The Journal of pharmacology and experimental therapeutics · 2022Article
- Individualized medication based on pharmacogenomics and treatment progress in children with IgAV nephritis.Frontiers in pharmacology · 2022Review
- Genetic Polymorphisms and the Clinical Response to Systemic Lupus Erythematosus Treatment Towards Personalized Medicine.Frontiers in pharmacology · 2022Review
- Characterization of Cytosolic GlutathioneDrug metabolism and disposition: the biological fate of chemicals · 2021Article
- Mechanism of Action and Efficacy of Immunosupressors in Lupus Nephritis.International journal of nephrology and renovascular disease · 2021Review
- Pharmacogenetics to optimize immunosuppressant therapy in systemic lupus erythematosus: a scoping review.PharmacogenomicsArticle
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectivesSystemic lupus erythematosus (SLE) is a systemic autoimmune disease. Cyclophosphamide (CYC) is a cytotoxic drug of a narrow therapeutic window that is commonly used in lupus nephritis (LN) treatment. However, 30-40% of patients experience CYC resistance. CYC inactivation is mediated by the glutathione S transferases (GSTs) superfamily: GST class A (GSTA) has the greatest activity and contains 5 isoenzymes. Polymorphisms of genes involved in the drug metabolism could alter the drug pharmacokinetics and effectiveness. CYC pharmacokinetics and pharmacogenomics are extensively studied in malignancies; however, scarce data are available about this issue in the autoimmune rheumatic diseases. Prediction of the drug response helps the achievement of the highest benefit-to-risk ratio. The aim of this case-control study was to address the association between GSTA1 polymorphism (-69C > T, rs3957356), and the rate of response to and side effects of intravenous CYC in LN patients.
methodsNinety-four patients were included and divided into matched groups: resistant and responsive. Genotyping was performed using restriction fragment length polymorphism method after amplification.
resultsA significant association between the TT genotype, and CYC resistance and partial response was observed. Concerning the recessive model, none of the patients within the TT group achieved complete remission. CYC side effects were more common with the polymorphism under the genotype, recessive model, and allele distributions. When patients' pre- and post-treatment characteristics were compared, patients with the TT genotype did not show any significant improvement.
conclusionLN patients with GSTA1 (-69C > T, rs3957356) TT genotype have the highest risk of CYC unresponsiveness and toxicity. Key-Points • LN patients with the wild genotype of GSTA1 have the greatest probability of achieving a complete renal response to IV CYC. • The homozygous GSTA1 (-69C > T, rs3957356) TT genotype is associated with the highest risk of LN unresponsiveness to IV CYC. • The homozygous GSTA1 (-69C > T, rs3957356) TT genotype is associated with the highest risk of CYC-related side effects.
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