激素耐药型与激素敏感型肾病综合征差异表达基因分析

Study on the differentially expressed genes of steroid-resistant and steroid-sensitive nephrotic syndrome

目的从基因水平探讨激素耐药型（steroid—resistant nephrotic syndrome，SRNS）和激素敏感型（steroid-sensitive nephrotic syndrome，SSNS）原发性肾病综合征分子遗传学机制。方法对原发性肾病综合征（SRNS患儿3例，SSNS患儿3例）和正常对照3名提取外周血单个核细胞总RNA；纯化mRNA，逆转录合成生物素标记的cRNA探针与基因芯片杂交；GCOS软件分析各组基因差异表达情况；层次聚类和Gene Ontology数据库进行生物信息学分析；定量PCR验证芯片的基因差异表达结果。结果与正常对照组相比较，与SRNS组和SSNS组相关的差异基因共157条；聚类分析显示SSNS组与对照组基因表达差异较小，SRNS组与前两者差异明显；功能分析发现与SRNS组相关的差异表达基因主要参与细胞核内生物学活动和细胞信号转导。结论不同临床和病理类型原发性肾病综合征涉及多个不同的差异基因和生物学途径，其中HLADRB4和CLNS1A基因可能在不同类型原发性肾病综合征发病机制中发挥重要作用。

Objective To identify the genes differentially expressed among the steroid-resistant nephrotic syndrome （SRNS）, steroid-sensitive nephrotic syndrome （SSNS） and normal children, and understand the molecular mechanism of SRNS. Methods Affymetrix mieroarray technology was used to obtain such a profile. The differentially expressed genes among these groups were identified based on signal- to-noise ratios by GCOS software; real-time PCR analysis was performed to confirm the mieroarray results. Results There were 157 genes differentially expressed among these groups. The genes up-regulated both in SRNS and SSNS were involved primarily in ionic transportation, immuno-signal transduction and apoptosis. In particular, CLNSIA gene was down regulated in SRNS but up regulated in SSNS. Conclusion Several differentially expressed genes, such as CLNS1A and HLA-DRB4 were found to be closely related to the pathogenesis of SRNS and SSNS. This DNA microarray analysis has provided some important clue to the molecular mechanism of SRNS.