Glutathione S transferases polymorphisms are independent prognostic factors in lupus nephritis treated with cyclophosphamide

Alexandra Audemard-Verger, Nicolas Martin Silva, Céline Verstuyft, Nathalie Costedoat-Chalumeau, Aurélie Hummel, Véronique Le Guern, Karim Sacré, Olivier Meyer, Eric Daugas, Cécile Goujard, Audrey Sultan, Thierry Lobbedez, Lionel Galicier, Jacques Pourrat, Claire Le Hello, Michel Godin, Rémy Morello, Marc Lambert, Eric Hachulla, Philippe VanhilleGuillaume Queffeulou, Jacky Potier, Jean Jacques Dion, Pierre Bataille, Dominique Chauveau, Guillaume Moulis, Dominique Farge-Bancel, Pierre Duhaut, Bernadette Saint-Marcoux, Alban Deroux, Jennifer Manuzak, Camille Francès, Olivier Aumaitre, Holy Bezanahary, Laurent Becquemont, Boris Bienvenu

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11 Scopus citations

Abstract

Objective To investigate association between genetic polymorphisms of GST, CYP and renal outcome or occurrence of adverse drug reactions (ADRs) in lupus nephritis (LN) treated with cyclophosphamide (CYC). CYC, as a pro-drug, requires bioactivation through multiple hepatic cytochrome P450s and glutathione S transferases (GST). Methods We carried out a multicentric retrospective study including 70 patients with proliferative LN treated with CYC. Patients were genotyped for polymorphisms of the CYP2B6, CYP2C19, GSTP1, GSTM1 and GSTT1 genes. Complete remission (CR) was defined as proteinuria 0.33g/day and serum creatinine 124 μmol/l. Partial remission (PR) was defined as proteinuria -1.5g/day with a 50% decrease of the baseline proteinuria value and serum creatinine no greater than 25% above baseline. Results Most patients were women (84%) and 77% were Caucasian. The mean age at LN diagnosis was 41 ± 10 years. The frequency of patients carrying the GST null genotype GSTT1-, GSTM1-, and the Ile!105Val GSTP1 genotype were respectively 38%, 60% and 44%. In multivariate analysis, the Ile!105Val GSTP1 genotype was an independent factor of poor renal outcome (achievement of CR or PR) (OR = 5.01 95% CI [1.02-24.51]) and the sole factor that influenced occurrence of ADRs was the GSTM1 null genotype (OR = 3.34 95% CI [1.064-10.58]). No association between polymorphisms of cytochrome P450s gene and efficacy or ADRs was observed. Conclusion This study suggests that GST polymorphisms highly impact renal outcome and occurrence of ADRs related to CYC in LN patients.

Original languageEnglish (US)
Article numbere0151696
JournalPloS one
Volume11
Issue number3
DOIs
StatePublished - Mar 2016

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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