439-P: A Promising Regulatory Role for MicroRNA-133b in Controlling Lipid Metabolism and Dyslipidemia Gene Expression in Diabetic Retinopathy: The 1000 Qataromics Cohort

A number of hyperglycemia- and dyslipidemia- triggered pathways, and numerous protein-encoding genes boosting the diabetic retinopathy (DR) progression. Evolving data suggests vast number of microRNAs(miRNAs) which exhibit no protein-coding capacity, are expressed and play key roles in DR pathogenesis.

Purpose: of this pilot is to identify the miRNAs involved in pathways altered in lipid metabolism and dyslipidemia and to explore the association of dyslipidemia with the progression of DR.

Methodology: 460 patients with diabetes type 2 (T2D) aged 23-77 years including 37 with DR and 490 matched healthy controls age range 18-74, from Qatar biobank cohort. The circulating miRNA profile was assessed in this pilot study. Logistic regression analysis was performed on the phenotypic data to investigate the level of association between A1C, low-density lipoproteins (LDL) and Triglycerides (TG) covariants and the miRNA expression profile in T2D with and without DR.

Results: The most broadly characterized miRNAs in lipid metabolism are miR-33a/b; however, we identified another three miRNAs (miR-133b, miR-142-3p and miR-483-5p) shared between LDL and TG phenotypes. In particular, miR-133b appeared to be directly linked to retinal degeneration identified through our miRNA-target disease interaction network analysis. Our results indicated that all three miRNAs are significantly associated with VEGFR2 mediated vascular permeability, insulin signaling, apoptosis, EGFR, TGF-Beta signaling, cellular senescence and degradation pathways leading to the DR initiation than development.

Conclusions: miRNAs are not only small regulators of lipid metabolism, but vital influencers in lipid homeostasis and lipoproteins formation and secretion. Dysregulation of these regulatory elements most likely augment the underlying metabolic flaws perceived in lipid disorders and related microvascular complications.