الفهرس 
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Abstract
Background: Type 2 diabetes mellitus (T2DM) is a major public health concern facing the world today. It is a complex disease involving both environmental and genetic contributing factors. The genetic variants in leptin and leptin receptor genes may play a major role in the pathogenesis of T2DM and its complications. In addition, recent studies suggested that the expression of biomolecules including microribonucleic acids (miRNAs) especially changes during the progression of T2DM, and its related complications, and suggestive of disease pathology. miRNAs are small noncoding RNA molecules which regulate the target gene expression post transcriptionally. Increasing studies have shown that miRNA play important roles in multiple biological pathways. For instance, aberrant expression of miRNA-224 plays a vital role in tumor biology in various types of human cancer.
Objective: This study aimed to assess serum miRNA-224 expression and determine its possible correlation with serum leptin levels and its genetic variant rs7799039 in Egyptian patients with T2DM and its diabetic complications. A major aim was to evaluate the association of both serum leptin levels, its genetic variant rs7799039 and miRNA-224 expression with the development of diabetic complications.
Methods: 100 T2DM patients and 105 healthy individuals were enrolled in the study. The biochemical, anthropometric, and physiometric parameters were evaluated. Serum leptin levels was measured by enzyme-linked immunosorbent assay (ELISA) technique. Leptin genotyping and miRNA-224 expression were performed using allelic-discrimination polymerase chain reaction and quantitative real-time PCR. Results were statistically analyzed to assess serum miRNA-224
Abstract
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expression and determine its possible correlation with serum leptin levels and its genetic variant rs7799039 in Egyptian patients with T2DM.
Results: T2DM patients had significantly elevated levels of glycated hemoglobin (HbA1C), fasting blood suger (FBS), post prandial blood sugar (PPBS), international normalization ratio (INR), creatinine, urea, cholesterol, triglyceride (TG) and low density lipoproteins (LDL) and significantly decreased high density lipoprotein (HDL) compared to healthy subjects. miRNA-224 expression was significantly upregulated in T2DM patients compared to healthy individuals p (<0.001), while serum leptin levels were significantly decreased p (<0.001) as compared to control group. miRNA-224 showed superior diagnostic potential for diabetes and predicted diabetic risk among non-diabetic groups. Leptin levels were inversely correlated with miRNA-224 in diabetic group.
Diabetic complications including retinopathy, neurological, eye complications, joint pain and cardiac disease were more frequent in T2DM patients than in control subjects. These differences were statistically significant at p (<0.05).
Leptin gene SNP rs7799039 was associated with an increased diabetic risk with A allele being more frequent in T2DM pateints than control subjects. The distribution of AA genotype and GA genotype of leptin SNP rs7799039 was higher in diabetic group than control one. In addition, AA+GA genotype carriers had significantly elevated HbA1C, FBS, PPBS, TG, LDL levels and upregulated miRNA-224 expression, and on the contrary, decreased serum leptin levels compared to GG homozygotes.
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Conclusion: Leptin levels and its rs7799039 genetic variant may play a role in increasing T2DM susceptibility. Moreover, miRNA-224 could be considered as a novel diabetes-associated miRNA which is highly expressed in the serum of T2DM patients.
Keywords: T2DM; leptin ; miRNA-224; SNP rs7799039.