Yee-Hsuan Chiou1, Lin-Yu Wang, Tzu-Hui Wang, Shiao-ping Huang. 1. Division of Pediatric Nephrology, Department of Pediatrics, Kaohsiung Veterans General Hospital, 386, Ta-Chung 1st Road, Zuoying District, Kaohsiung City, Taiwan. chysn@ms6.hinet.net
Abstract
BACKGROUND: Idiopathic nephrotic syndrome (INS) is the most frequent type of nephrotic syndrome that occurs in children. Its response to treatment with steroids varies. The aim of this study was to analyze the correlation between steroid metabolism-related genes and the response to steroid treatment. METHODS: The patient cohort comprised 74 children with INS, of whom were 58 steroid-sensitive (SS) cases and 16 steroid-resistant (SR) cases. The genetic polymorphisms analyzed were those of the CYP3A5 gene (A6986G) and ABCB1 gene (C1236T, G2677T/A, and C3435T), and the polymorphisms between SS and SR children were compared. RESULTS: C1236T in ABCB1 was associated with steroid resistance in INS children [odds ratio (OR) 2.65, 95 % confidence interval (CI) 1.01-6.94; p = 0.042] The frequency of the T allele was significantly higher in SR subjects than in SS subjects (0.81 vs. 0.62, respectively). A6986G in CYP3A5 showed a trend of association, but this association did not reach statistical significance (OR 2.63, 95 % CI 0.94-7.37; p = 0.059). No significant correlation was found between treatment response and G2677T/A or C3435T in ABCB1. CONCLUSIONS: Our results indicate that among our pediatric patients with INS the C1236T polymorphism in the ABCB1 gene was associated with steroid resistance, while the A6986G polymorphism in the CYP3A5 gene showed a trend of association, but did not reach statistical significance, requiring further analysis.
BACKGROUND:Idiopathic nephrotic syndrome (INS) is the most frequent type of nephrotic syndrome that occurs in children. Its response to treatment with steroids varies. The aim of this study was to analyze the correlation between steroid metabolism-related genes and the response to steroid treatment. METHODS: The patient cohort comprised 74 children with INS, of whom were 58 steroid-sensitive (SS) cases and 16 steroid-resistant (SR) cases. The genetic polymorphisms analyzed were those of the CYP3A5 gene (A6986G) and ABCB1 gene (C1236T, G2677T/A, and C3435T), and the polymorphisms between SS and SR children were compared. RESULTS:C1236T in ABCB1 was associated with steroid resistance in INS children [odds ratio (OR) 2.65, 95 % confidence interval (CI) 1.01-6.94; p = 0.042] The frequency of the T allele was significantly higher in SR subjects than in SS subjects (0.81 vs. 0.62, respectively). A6986G in CYP3A5 showed a trend of association, but this association did not reach statistical significance (OR 2.63, 95 % CI 0.94-7.37; p = 0.059). No significant correlation was found between treatment response and G2677T/A or C3435T in ABCB1. CONCLUSIONS: Our results indicate that among our pediatric patients with INS the C1236T polymorphism in the ABCB1 gene was associated with steroid resistance, while the A6986G polymorphism in the CYP3A5 gene showed a trend of association, but did not reach statistical significance, requiring further analysis.
Authors: E G Schuetz; J D Schuetz; W M Grogan; A Naray-Fejes-Toth; G Fejes-Toth; J Raucy; P Guzelian; K Gionela; C O Watlington Journal: Arch Biochem Biophys Date: 1992-04 Impact factor: 4.013
Authors: Thomas Illmer; Ulrich S Schuler; Christian Thiede; Ute I Schwarz; Richard B Kim; Sebastian Gotthard; Daniel Freund; Ulrike Schäkel; Gerhard Ehninger; Markus Schaich Journal: Cancer Res Date: 2002-09-01 Impact factor: 12.701
Authors: D R Nelson; L Koymans; T Kamataki; J J Stegeman; R Feyereisen; D J Waxman; M R Waterman; O Gotoh; M J Coon; R W Estabrook; I C Gunsalus; D W Nebert Journal: Pharmacogenetics Date: 1996-02
Authors: Eric Thervet; Dany Anglicheau; Barry King; Marie-Hélène Schlageter; Bruno Cassinat; Philippe Beaune; Christophe Legendre; Ann K Daly Journal: Transplantation Date: 2003-10-27 Impact factor: 4.939
Authors: P H Beaune; P G Kremers; L S Kaminsky; J De Graeve; A Albert; F P Guengerich Journal: Drug Metab Dispos Date: 1986 Jul-Aug Impact factor: 3.922
Authors: Yvonne S Lin; Amy L S Dowling; Sean D Quigley; Federico M Farin; Jiong Zhang; Jatinder Lamba; Erin G Schuetz; Kenneth E Thummel Journal: Mol Pharmacol Date: 2002-07 Impact factor: 4.436
Authors: Most Nazma Parvin; Md Abdul Aziz; Sikder Nahidul Islam Rabbi; Mir Md Abdullah Al-Mamun; Mohammed Hanif; Md Saiful Islam; Mohammad Safiqul Islam Journal: J Adv Res Date: 2021-02-17 Impact factor: 10.479