Abstract 18175: LncRNA in Monocytes of Patients With Type 2 Diabetes and Established Cardiovascular Disease Modulate the Expression of Protein-Coding Genes

Abstract

Introduction: Monocytes contribute to cardiovascular complications of type 2 diabetes (T2D) through various mechanisms. Objectives: We investigated diabetes-induced changes in long non-coding RNAs (lncRNA) from monocytes of patients with T2D and established cardiovascular disease. Methods: We performed polyA capture and paired-end RNA sequencing of monocytes from 120 patients with T2D and 37 non-diabetes controls. Monocytes were sorted using FACSAria2 flow cytometer. Alignments and gene counts were done with STAR to reference GRCh38 using Gencode (v41) gene annotations. The batch correction was done with CombatSeq and differential expression analysis with EdgeR. The false discovery was controlled with the Benjamini-Hochberg procedure. Pathway analysis was done with the IPA software using differentially expressed genes (DEGs) with a p-value < 0.05. Co-expression analysis was done with cdsR and Cytoscape. Results: We found two significantly upregulated lncRNAs in monocytes from diabetes patients (ENSG00000287255 and ENSG00000289424, FDR = 0.035). Pathway analysis on DEGs revealed a network affecting cellular movement, growth, and development that includes directly interacting plasma membrane genes ITGB4 and CDH1, nuclear genes HIF1a, ZEB1, ETS1, TWIST1, SNAI2, NFKB complex, and lncRNA genes SNHG29 and FBXL19-AS1 (p < 1*10^ -25 ). Analysis within T2D patients revealed one lncRNA upregulated only in monocytes from patients with microvascular disease (ENSG00000261654 on chr1, FDR =0.022). Interestingly, co-expression analysis uncovered correlated expression clusters between lncRNAs and protein-coding genes, with one interesting interaction identified between the highly connected MCR1 and SNHG7, a lncRNA shown to respond to IGF-1 (insulin-like growth factor 1) . Conclusion: Monocytes from patients with diabetes have differentially expressed lncRNA genes that potentially impact diabetes-related pathways.