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

被引：16

作者：

Audemard-Verger, Alexandra ^{[1
]}

Silva, Nicolas Martin ^{[1
]}

Verstuyft, Celine ^{[2
]}

Costedoat-Chalumeau, Nathalie ^{[3
]}

Hummel, Aurelie ^{[4
]}

Le Guern, Veronique ^{[3
]}

Sacre, Karim ^{[5
]}

Meyer, Olivier ^{[6
]}

Daugas, Eric ^{[7
]}

Goujard, Cecile ^{[8
]}

Sultan, Audrey ^{[1
]}

Lobbedez, Thierry ^{[9
]}

Galicier, Lionel ^{[10
]}

Pourrat, Jacques ^{[11
]}

Le Hello, Claire ^{[12
]}

Godin, Michel ^{[13
]}

Morello, Remy ^{[14
]}

Lambert, Marc ^{[15
]}

Hachulla, Eric ^{[15
]}

Vanhille, Philippe ^{[16
]}

Queffeulou, Guillaume ^{[17
]}

Potier, Jacky ^{[17
]}

Dion, Jean-Jacques ^{[18
]}

Bataille, Pierre ^{[19
]}

Chauveau, Dominique ^{[11
]}

Moulis, Guillaume ^{[20
,21
,22
]}

Farge-Bancel, Dominique ^{[23
]}

Duhaut, Pierre ^{[24
]}

Saint-Marcoux, Bernadette ^{[25
]}

Deroux, Alban ^{[26
]}

Manuzak, Jennifer ^{[27
]}

Frances, Camille ^{[28
]}

Aumaitre, Olivier ^{[29
]}

Bezanahary, Holy ^{[30
]}

Becquemont, Laurent ^{[2
]}

Bienvenu, Boris ^{[1
]}

机构：

[1] CHU Caen, Dept Internal Med, F-14000 Caen, France

[2] Hop Kremlin Bicetre, Dept Pharmacol, Le Kremlin Bicetre, France

[3] Univ Paris 05, Hop Cochin, AP HP, Dept Internal Med, Paris, France

[4] Hop Necker Enfants Malad, Dept Nephrol, Paris, France

[5] Hop Bichat Claude Bernard, Dept Internal Med, F-75877 Paris, France

[6] Hop Bichat Claude Bernard, Dept Rheumatol, F-75877 Paris, France

[7] Hop Bichat Claude Bernard, Dept Nephrol, F-75877 Paris, France

[8] Hop Kremlin Bicetre, Dept Internal Med, Le Kremlin Bicetre, France

[9] CHU Caen, Dept Nephrol, F-14000 Caen, France

[10] Hop St Louis, Dept Clin Immunopathol, Paris, France

[11] CHU Toulouse, Dept Nephrol & Clin Immunol, Toulouse, France

[12] CHU Caen, Dept Vasc Med, F-14000 Caen, France

[13] CHU Rouen, Dept Nephrol, Rouen, France

[14] CHU Caen, Biostat Unity, F-14000 Caen, France

[15] CHU Lille, Dept Internal Med, F-59037 Lille, France

[16] CH Valenciennes, Dept Nephrol, Valenciennes, France

[17] CH Cherbourg, Dept Nephrol, Cherbourg, France

[18] CH Charleville Meziere, Dept Nephrol, Charleville Meziere, France

[19] CH Boulogne Sur Mer, Dept Nephrol, Boulogne Sur Mer, France

[20] CHU Toulouse, Dept Internal Med, Toulouse, France

[21] Univ Toulouse, INSERM, UMR 1027, Toulouse, France

[22] CIC 1436, Toulouse, France

[23] Hop St Louis, Dept Internal Med, Paris, France

[24] CHU Amiens, Dept Internal Med, Amiens, France

[25] Hop Aulnay Sous Bois, Dept Rheumatol, Aulnay Sous Bois, France

[26] CHU Grenoble, Dept Internal Med, F-38043 Grenoble, France

[27] Inst Cochin, Dept Immunol, Paris, France

[28] Hop Tenon, Dept Dermatol, F-75970 Paris, France

[29] CHU Clermont Ferrand, Dept Internal Med, Clermont Ferrand, France

[30] CHU Limoges, Dept Internal Med, Limoges, France

来源：

PLOS ONE | 2016年 / 11卷 / 03期

关键词：

PULSE CYCLOPHOSPHAMIDE; GENETIC-POLYMORPHISM; ERYTHEMATOSUS; PREVALENCE; EXPRESSION; PHARMACOKINETICS; PREDICTOR; MORBIDITY; TOXICITY; THERAPY;

D O I：

10.1371/journal.pone.0151696

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

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 mu mol/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.

引用

页数：9

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