Document Details
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Document Type |
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Thesis |
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Document Title |
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Long non-coding RNAs and epigenetic codes implications on Ghrelin gene expression in Type 2 Diabetes Mellitus تأثير الأحماض النووية الريبوزية الطويلة الغيرمشفرة وشفرات ما فوق الجينات على التعبير الجيني لمورث الجريلين لدى مرضى السكري من النوع الثاني |
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Subject |
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Faculty of Science |
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Document Language |
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Arabic |
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Abstract |
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Long non-coding RNAs (lncRNAs) have an important role in many biological processes that are associated with several chronic diseases including Type 2 Diabetes Mellitus (T2DM). The hormone ghrelin (GHRL) has critical roles in the regulation of several pathways that are linked to the progression of T2DM. The aim of this project was to identify novel circulating lncRNAs located in the region of the GHRL gene as blood-based biomarkers and to understand the role of epigenetic changes in T2DM etiology and progression. Bioinformatics analysis was used to identify lncRNAs-GHRL candidates. The expression level of lncRNAs-GHRL and GHRL mRNA in 71 diabetic patients and 32 non-diabetic controls were determined using Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) method. Receiver Operating Characteristic (ROC) curve analysis was performed to evaluate the discriminatory power of the candidate lncRNAs-GHRL and GHRL mRNA as biomarkers for T2DM. Fasting blood glucose (FBG), glycated hemoglobin (HbA1c), total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), very low-density lipoprotein (VLDL), albumin, creatinine, urea, and uric acid levels were measured using standard assays. Linear regression analysis and Pearson coloration coefficient were performed to evaluate the correlation between lncRNAs-GHRL expression and levels of lipid profile. Quantitative screening of histone H3 modifications were performed using colorimetric assays that detect 22 different histone modifications including dimethyl H3K4 (H3K4me2) in the serum of 39 participants (29 diabetics and 10 non-diabetic subjects). The expression profiles demonstrated that the expression levels of lnc-GHRL-3:2, lnc-GHRL-3:3, GHRLOS, LINC00852, and GHRL mRNA were significantly downregulated in the diabetic patients compared to the non-diabetic controls (P < 0.0001). The values of the area under the curve (AUC) for lnc-GHRL-3:2, lnc-GHRL-3:3, GHRLOS, LINC00852, and GHRL mRNA were 0.90, 0.90, 0.96, 0.98 and 0.90; respectively. The results showed that the expression levels of the novel lncRNAs-GHRL and GHRL mRNA were significantly positively associated with HDL and significantly negatively correlated with the level of FBG, HbA1c, TC, TG, LDL, VLDL, uric acid, and urea (P ≤ 0.05). No association was observed between lncRNAs-GHRL with creatinine level. No significant differences were detected in the level of the 22 histone H3 modifications between T2DM patients and the non-diabetic control which suggests that there was no association between histone H3 modifications and T2DM. In conclusion, the results revealed that lnc-GHRL-3:2, lnc-GHRL-3:3, GHRLOS, LINC00852, and GHRL mRNA are novel biomarkers associated with T2DM and they might have regulatory roles in the development of the disease. Also, the expression of lncRNAs-GHRL and GHRL mRNA might have a potential role in the regulation of lipid metabolism in patients with T2DM. |
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Supervisor |
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Prof. Rowyda Nawwaf Al-Harithy |
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Thesis Type |
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Doctorate Thesis |
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Publishing Year |
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1443 AH
2022 AD |
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Added Date |
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Monday, January 16, 2023 |
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Researchers
| داليا محمد عنبري | Anbari, Dalia Mohammed | Researcher | Doctorate | |
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