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The GSTA1 polymorphism and cyclophosphamide therapy outcomes in lupus nephritis patients
- Source :
- Clinical Immunology. 160:342-348
- Publication Year :
- 2015
- Publisher :
- Elsevier BV, 2015.
-
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.
- 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
Subjects
Details
- ISSN :
- 15216616
- Volume :
- 160
- Database :
- OpenAIRE
- Journal :
- Clinical Immunology
- Accession number :
- edsair.doi.dedup.....8af950a1e644e963ff5a7b89a6c0d650