Do glutathione-S-transferase polymorphisms influence response to intravenous cyclophosphamide therapy in idiopathic neph
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ORIGINAL ARTICLE
Do glutathione-S-transferase polymorphisms influence response to intravenous cyclophosphamide therapy in idiopathic nephrotic syndrome? Sheetal V. Sharda & Sanjeev Gulati & Gaurav Tripathi & Tabrez Jafar & Alok Kumar & Raj Kumar Sharma & Suraksha Agrawal
Received: 5 September 2007 / Revised: 9 April 2008 / Accepted: 14 April 2008 / Published online: 2 July 2008 # IPNA 2008
Abstract The response to cyclophosphamide (CP) is variable and difficult to predict in children with idiopathic nephrotic syndrome (INS). The polymorphic expression of glutathione-S-transferase (GST) may affect the remission rate after CP therapy. In this study, we evaluated the correlation of GST polymorphism and response to CP in INS. We studied GST polymorphism in 74 children with steroid-sensitive (44) and steroid-resistant (30) INS receiving intravenous cyclophosphamide (IVCP) therapy. We correlated GSTM1, GSTT1, and GSTP1 genotypes with response to IVCP. Thirty-seven (50%) out of 74 children responded to CP therapy. A synergistic effect of three genotypic combinations showed significant correlation with remission in the steroidsensitive group. These combinations were GSTP1 and GSTM1 null genotype (p=0.013) and GSTP1 together with GSTM1 and GSTT1 null genotypes (p=0.026). Further, a significant difference was observed with a combination of GSTM1 and GSTT1 null genotypes and Val105 polymorphism. No association was observed among steroid-resistant S. V. Sharda : G. Tripathi : T. Jafar : S. Agrawal Department of Medical Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareli Road, Lucknow, UP 226014, India S. Gulati : A. Kumar : R. K. Sharma Department of Nephrology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareli Road, Lucknow, UP 226014, India S. Gulati (*) Department of Nephrology, Fortis Institute of Renal Sciences and Transplantation, VasantKunj, New Delhi 1100070, India e-mail: [email protected]
patients. Our results indicate that among children with steroidsensitive NS, there is an association with response to IVCP therapy and combination of GSTP1 Val105 polymorphism and the null genotypes of GSTT1 and GSTM1. GST polymorphism may be of significance in the management of children with INS receiving CP therapy. Keywords Nephrotic syndrome (NS) . Immunosuppressant therapy . Glutathione-S-transferase . Polymorphism . Cyclophosphamide
Introduction Idiopathic nephrotic syndrome (INS) is one of the commonest kidney disorders in children. Although the majority of these children respond to steroids, 40–50% show frequent relapses (FR) or steroid dependence (SD) [1]. Increasing dose of steroids leads to toxicity, requiring the use of potentially toxic drugs such as cyclophosphamide, chlorambucil, and cyclosporin A to achieve long-term remission. Many studies have shown that the best longterm remission rates are achieved with cyclophosphamide (CP) [2–6]. The average response rate to CP in various studies ranges from 28% to 75% in SD and from 24% to 70% in FR at 1–3 years [3]. Intr
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