Journal
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
Volume 61, Issue 13, Pages -Publisher
ASSOC RESEARCH VISION OPHTHALMOLOGY INC
DOI: 10.1167/iovs.61.13.12
Keywords
NLRP3; methylation; diabetic retinopathy
Categories
Funding
- National Natural Science Foundation of China [81970813]
- Natural Science Foundation of Guangdong Province [2018A030313635]
- Guangzhou Municipal Science and Technology Project [201904010062]
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PURPOSE. To identify and validate key genes that could provide a new perspective for genetic marker screening of diabetic retinopathy (DR). METHODS. The gene expression and DNA methylation profiles were obtained from the Gene Expression Omnibus. Differential expression analysis was conducted using the limma package, and then the functions of the differentially expressed genes (DEGs) were analyzed using the DAVID database, followed by protein-protein interaction (PPI) networks using Cytoscape software. We employed the Sequenom MassARRAY system to detect the promoter methylation levels of the candidate genes in peripheral blood mononuclear cells from 32 healthy individuals and 94 patients with type 2 diabetes mellitus (T2D; 64 with DR and 30 without DR) and in fibrovascular membranes (FVMs) from three proliferative DR patients and three controls with idiopathic epiretinal membranes. The mRNA levels of candidate genes were further confirmed via real-time polymerase chain reaction. RESULTS. A significant enrichment of 5906 DEGs was found in immune and inflammatory responses. TGFB1, CCL2, and TNFSF2 were identified as the top three core genes associated with NLRP3 inflammation in PPI networks. These genes have relatively low levels of promoter methylation, which have been validated in peripheral blood mononuclear cells and FVMs from DR patients, and the methylation levels were found to be negative correlated with the mRNA levels and HbA1c levels in T2D patients. CONCLUSIONS. Overall, these data indicate that promoter hypomethylation of NLRP3, TGFB1, CCL2, and TNFSF2 may increase the risk of DR in the Chinese Han population, indicating that these genes might serve as potential targets for the detection and treatment of DR.
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