title: Genetic variations of the NR3C1 gene in children with sporadic nephrotic syndrome.
abstract: Previous studies have demonstrated that the genetic variations of glucocorticoid receptor gene (NR3C1) are associated with both familial steroid resistance and acquired steroid resistance in some diseases, such as Cushing's disease, leukemia, lupus nephritis, and female pseudohermaphroditism. In this study, we examined the genetic variations of NR3C1 in 35 children with sporadic steroid-resistant nephrotic syndrome (SRNS), and in 83 cases with sporadic steroid-sensitive NS (SSNS) using polymerase chain reaction, denaturing high-performance liquid chromatography and DNA sequencing, and analyzed possible associations between NR3C1 variants and steroid resistance in sporadic NS. No causative mutations were found; however, six previously identified and six novel polymorphisms, 1206C > T, 1374A > G, 2382C > T, 2193T > G, IVS7-68_-63delAAAAAA, and IVS8-9C > G, were detected. Two novel haplotypes, [1374A > G; IVS7-68_-63delAAAAAA; IVS8-9C > G; 2382C > T] and [1896C > T; 2166C > T; 2430T > C], of NR3C1 were also identified in sporadic NS and controls. The odds ratios (95% Confidence Interval) for the two novel NR3C1 haplotypes in the sporadic nephrotic children at risk of steroid resistance were 4.970 (0.889-27.788) and 2.194 (0.764-6.306), respectively, but the association between NR3C1 haplotypes and steroid resistance was not significant. Further studies on the possible association between the two novel NR3C1 haplotypes and steroid resistance in sporadic NS in larger cohorts are required.
authors.affiliation: Department of Pediatrics, Peking University First Hospital, Beijing, PR China.
authors.forename: Jianwei
authors.initials: J
authors.lastname: Ye
authors.forename: Zihua
authors.initials: Z
authors.lastname: Yu
authors.forename: Jie
authors.initials: J
authors.lastname: Ding
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
authors.forename: Jianping
authors.initials: J
authors.lastname: Huang
authors.forename: Yong
authors.initials: Y
authors.lastname: Yao
authors.forename: Huijie
authors.initials: H
authors.lastname: Xiao
authors.forename: Jiyun
authors.initials: J
authors.lastname: Yang
authors.forename: Ying
authors.initials: Y
authors.lastname: Shen
authors.forename: Qun
authors.initials: Q
authors.lastname: Meng
mesh_terms: D000293:Adolescent; D001483:Base Sequence; D002648:Child; D002675:Child, Preschool; D002851:Chromatography, High Pressure Liquid; D004351:Drug Resistance; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007223:Infant; D008297:Male; D009404:Nephrotic Syndrome / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011489:Protein Denaturation; D011965:Receptors, Glucocorticoid / Q000235:genetics*; D013256:Steroids / Q000627:therapeutic use
chemical_list: C497713:NR3C1 protein, human; D011965:Receptors, Glucocorticoid; D013256:Steroids