1.Study On Differentially Expressed Genes Of Steroid-resistant And Steroid-sensitive Nephrotic Syndrome 2.NPHS2 Variation In South Chinese Children With Late Steroid-resistant Nephrotic Syndrome

Objectives:Primary nephrotic syndrome (PNS) characterized by edema, proteinuria, hyperlipidemia and low serum albumin, is a common disease in pediatric nephrology. Most children with NS are sensitive to regular steroid treatment (steroid sensitive nephrotic syndrome, SSNS) with eusemia, but approximately 20% NS children are resistant to the treatment (steroid resistant nephrotic syndrome, SRNS) with a possibly gradual progression to end-stage renal disease (ESRD). However the underlying mechanism of SRNS has not been completely elucidated yet. Many studies has proved that genetic variation is one of the causes of SRNS. The differentially expressed genes were analyzed in 9 Chinese children with SSNS, SRNS and normal controls to explore the possibly causative genes with NS and make an approach to genetic pathogenesis of SRNS.Methods:3 groups of children were included in this study. Genomic DNA was directly isolated from peripheral blood samples, and differentially expressed genes were analyzed in peripheral blood mononuclear cell (PBMC) of SRNS, SSNS and controls children(each group including 3 persons) by Affymetrix genechip microarray. The software GCOS was used for microarray experiment data analysis. The ratio value is calculated for each gene compared with the gene of controls. A ratio value greater then 2.0 or less than 0.5 is considered a significant change. Significant differentially expressed genes were analyzed by Gostate online, and establish an SRNS or SSNS related gene differential expression profile for GO analysis,to sereen the SRNS or SSNS related gene group finally.Results:1. On the Affymetrix platform showed detectable expression, of which 157 genes were found with close relation to PNS. Compared to normal controls, 60 genes up regulated and 8 genes down regulated in SRNS group; 5 genes were selected radomly to verificated by realtime PCR. The results revealed similar values to the ratio values generated by the microarrays.2. The genes up-regulated both in SRNS and SSNS were involved primarily in ionic transportation, immuno-signal transduction and apoptosis.Especially, CLNS1A gene down regulated in SRNS but up regulated in SSNS, and HLA-DRB4 gene down regulated in SSNS obviously. 15 pathways were hitted to related to SRNS, of which CTNNB1 gene were involved in 8 pathways, especially in TGF-βpathway and wnt pathway.Conclusion:1. PNS is the common consequene of multiple genes. Several functional gene groups participate and play vital roles in the PNS pathogenisis; Such as ionic transportation, immuno-signal transduction and apoptosis relatedgene;2. Several differentially expressed genes, such as CLNS1A and HLA-DRB4 were found to be closely relevant to pathogenesy of SRNS and SSNS. Some important clue to PNS were provided by DNA microarry. CTNNB1 gene may play an key role in TGF-βpathway and wnt pathway for SRNS children with FSGS.