Differentially methylated genes in children with steroid-dependent or steroid-sensitive nephrotic syndrome:A bioinformatic analysis / 医学研究生学报

ABSTRACT

Objective Few researches have been reported on the gene methylation in children with steroid-sensitive nephrot-ic syndrome (SSNS) or steroid-dependent nephrotic syndrome (SDNS).This study aimed to investigate the possible pathogenesis and therapeutic target of SSNS and SDNS by screening differentially methylated genes ( DMGs) and bioinformatic analysis using DNA meth-ylation microarray. Methods This study included 3 hospitalized children with SSNS and another 4 with SDNS, all treated with full dose of prednisone ( 2 mg per kilogram of the body weight per day or 60 mg per m2 per day).Negative urine protein was achieved within 4 weeks in the former group , while the latter , though sensitive to hor-monal therapy , relapsed within 2 weeks after drug withdrawal or dose reduction .DNA was extracted from the peripheral blood of the patients in both groups for screening DMGs and bioinformatic analysis using DNA methylation microarray . Results Compared with the patients with SSNS, 318 DMGs were found in the SDNS group , among which 193 were hypermethylated and the other 125 hypomethylated .These abnormal genes were mainly located in the open reading frame of DNA and the CpG island region .DMGs were mainly involved in Rho guanyl-nucleotide exchange factor activity , nucleoside-triphosphatase regulator activity , GTPase activator activity , and other molecular functions .The biological processes were chiefly associ-ated with the regulation of the generation of precursor metabolites and energy , antigen processing and presentation , regulation of Rho and Ras protein signal transduction , lamellipodium assembly , regeneration , and other biological processes .The cell composition was mainly related to MHC protein complexes , perichromatin fibrils , and the MHC class I protein complex .Analysis of the KEGG signaling pathway showed that DMGs participated in 9 signaling pathways , involving type I diabetes , starch and sucrose metabolism , allograft re-jection, autoimmune thyroid disease , and others. Conclusion The heterogeneity of methylation is widespread in children with SDNS and may be one of the causes of steroid dependence , which has provided a basis for searching for potential therapeutic targets .