395-P: Identification of Key Genes and Transcriptional Factors Associated with Podocyte Functions in Human Diabetic Nephropathy

Background: Direct podocyte injury in Diabetic nephropathy (DN) leads to proteinuria, glomerular hypertrophy, and accumulation of extra cellular matrix. By using six publicly available gene expression profiles from early DN, DN, advanced DN, and healthy controls. We have analyzed each of the DN stages against healthy controls and also analyzed the datasets using network inference technique to identify genes playing key role in DN pathogenesis. Methodology: We performed modular repertoire analysis for each dataset separately, then, we performed meta-analysis by merging the datasets to obtain robust differentially expressed genes (DEG). Network inference technique was used to explore and detect novel associations between the DEG and to infer the interaction between the set of genes using mutual information (MI) measure. Statistically significant interactions were selected using a threshold p Results: A total of 193 samples from the gene expression datasets of human kidney tissues were used, where 79 samples from DN, 21 of advanced DN, 10 early DN, 10 DKD, and 73 from controls. Several key genes have been identified in addition to a highly connected small cluster of genes enriched for podocyte differentiation. Two transcription factors, DACH1 and WT1, are important for podocyte differentiation and proper kidney function have been identified. Also, the expression level of TYRO3 which is a podocyte protective factor increased in early DN but was decreased as the disease progressed, per our analysis. Conclusion: This meta-analysis found some of the key genes associated with DN. The level of contribution and relevance of the identified genes in the pathogenesis of DN should be functionally analyzed. Disclosure A. S. Akil: None. S. Subash padmajeya: None. K. Fakhro: None. T. Habib: None. Funding Qatar National Research Fund (NPRP9-229-3-041)