1. The GSTA1 polymorphism and cyclophosphamide therapy outcomes in lupus nephritis patients
- Author
-
Ying Zhu, Xiaoye Zhu, Lin-yun Lai, Shanyan Lin, Yong Gu, Chuanming Hao, Qionghong Xie, Miao Zhao, Jun Xue, Yuan-Cheng Chen, and Hong-Na Wang
- Subjects
Adult ,Male ,Heterozygote ,medicine.medical_specialty ,Cyclophosphamide ,Immunology ,Lupus nephritis ,Single-nucleotide polymorphism ,Gastroenterology ,Young Adult ,Pharmacokinetics ,Polymorphism (computer science) ,Internal medicine ,Genotype ,medicine ,Humans ,Immunology and Allergy ,Allele ,Aged ,Glutathione Transferase ,Volume of distribution ,Polymorphism, Genetic ,business.industry ,Remission Induction ,Middle Aged ,medicine.disease ,Lupus Nephritis ,Treatment Outcome ,Pharmacogenetics ,Female ,business ,Immunosuppressive Agents ,medicine.drug - Abstract
Pulsed low-dose cyclophosphamide (CTX) therapy has become a very effective approach in improving the clinical outcomes of lupus nephritis (LN) patients. However, variations of CTX therapeutic outcomes in LN patients are incompletely understood. We investigated the contributions of known allelic variants to CTX therapy outcomes in 77 LN patients. Then, 22 out of the 77 patients were randomly enrolled to evaluate the pharmacokinetic profiles. LN patients with a GSTA1*A mutation (CT heterozygous) had more risk of non-remission (44% vs. 20%, P=0.005). Pharmacokinetic data indicated that patients with a GSTA1*A heterozygous variant had a lower exposure to 4-hydroxycyclophosphamide (4OHCTX) compared to wild-type patients (AUC4OHCTX: 12.8 (9.8, 19.5) vs. 27.5 (18.1, 32.8) h mg/l, P=0.023). Clinical remission was significantly related to higher exposure of 4OHCTX (P=0.038). In conclusion, LN patients with GSTA1*A heterozygous genotypes had poor CTX treatment remission due to less exposure to activated metabolites of CTX.
- Published
- 2015