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Multicenter Study
. 2016 Mar 22;11(3):e0151696.
doi: 10.1371/journal.pone.0151696. eCollection 2016.

Glutathione S Transferases Polymorphisms Are Independent Prognostic Factors in Lupus Nephritis Treated with Cyclophosphamide

Alexandra Audemard-Verger  1 , Nicolas Martin Silva  1 , Céline Verstuyft  2 , Nathalie Costedoat-Chalumeau  3 , Aurélie Hummel  4 , Véronique Le Guern  3 , Karim Sacré  5 , Olivier Meyer  6 , Eric Daugas  7 , Cécile Goujard  8 , Audrey Sultan  1 , Thierry Lobbedez  9 , Lionel Galicier  10 , Jacques Pourrat  11 , Claire Le Hello  12 , Michel Godin  13 , Rémy Morello  14 , Marc Lambert  15 , Eric Hachulla  15 , Philippe Vanhille  16 , Guillaume Queffeulou  17 , Jacky Potier  17 , Jean-Jacques Dion  18 , Pierre Bataille  19 , Dominique Chauveau  11 , Guillaume Moulis  20 , Dominique Farge-Bancel  21 , Pierre Duhaut  22 , Bernadette Saint-Marcoux  23 , Alban Deroux  24 , Jennifer Manuzak  25 , Camille Francès  26 , Olivier Aumaitre  27 , Holy Bezanahary  28 , Laurent Becquemont  2 , Boris Bienvenu  1
Affiliations
Multicenter Study

Glutathione S Transferases Polymorphisms Are Independent Prognostic Factors in Lupus Nephritis Treated with Cyclophosphamide

Alexandra Audemard-Verger et al. PLoS One. .

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.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

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