The role of mikrornas in hashimoto thyroiditis
2017
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Advisor: Yrd. Doç. Dr. Alper Han Çebi
Abstract (EN)
microRNAs (miRNAs) are small noncoding 18 to 24 nucleotides long RNA molecules, that have emerged in recent years. Most of miRNAs are found in the cells but they can be found extracellular area, body fluids and blood. miRNAs are regulatory in processes such as cell proliferation, differentiation, metabolic processes, apoptosis, inflammation and regulation of immunological processes. Observations made in various studies have shown that miRNAs found in human plasma have high stability and miRNA expression pattern analysis performed in these samples may provide useful information on the status of various diseases. In addition to the samples which are obtained from solid tissues, miRNAs can also be determined in patient serum / plasma, providing a fairly easy sampling of diseases that require the use of invasive techniques. Any disease, cell type or tissue type mediated by gene or protein synthesis deficiency may constitute miRNA-based targets. miRNAs are developmentally important because they have a regulatory role in the production of protein by messenger RNAs, which is therapeutically important. HT is one of the most common autoimmune and endocrine disease which characterized by the production of Anti-TPO and Anti-TG antibodies, which result in the breakdown of T and B lymphocytes by invading thyroid tissue. Scientific studies in recent years show that miRNAs have an important role in controlling the immune system. It is thought that HT activates lymphocytes that infiltrate the thyroid tissue. Thus, identification of the circulatory miRNA may provide important and novel information in clinical situations and disease pathogenesis. At the time of new diagnosis in Hashimoto thyroiditis and euthyroid period of the same patients' miRNA profile has not been studied yet. We therefore aimed to determine the miRNA expression levels at the time of new diagnosis and control period when the same patients were euthyroidized and to determine whether there is a difference in expression level between healthy control group and the patients' expression level. We are planning to make a contribution to the literature by presenting a new perspective on the pathogenesis of HT that has not yet fully attained enlightenment; And we expect that this new perspective will open new horizons to current HT treatment. We took blood from 34 patient who were diagnosed as Hashimoto thyroiditis newly who came to the Endocrinology Polyclinic in Karadeniz Technical University Medicine Faculty, and were taken blood again 3 months after when they were euthyroid. And blood samples were taken in tube with EDTA from 33 voluntary individuals who were in agreement with the gender and age group of the patients who did not have any health problems after the examinations performed at the endocrinology polyclinic. Expression levels of 5 different miRNAs (mir-22, miR-141, miR-155, miR-375, miR-451) which were known to be connected autoimmunity were revealed by previous publications were studied in the patient and control group. To quantitatively determine miRNA expression levels between patient and control groups, RT-PCR data were analyzed using the Qiagene Gene Globe Data Analysis Center portal ΔΔCt module (http://www.qiagen.com/us/shop/genes-and-pathways/data-analysis-center-overview-page/). In order to normalize the data, "Global CT Mean of expressed miRNAs" was used in the same analysis center. Relation of expression levels between groups was also determined by the system by the Student T test and p <0.05 was considered significant. Qualitative data are number and percentage; Measured data are presented with mean standard deviation and minimum maximum values. The relationship between TSH and miRNA expression level between the first diagnostic moment of the patient group and the control period after 3 months was calculated by Spearman correlation analysis. The data were analyzed in IBM SPSS Statistics for Windows 23.0 statistical package program. The conclusion of our study is that circulating miRNAs in different levels of plasma may be associated with disease activity in HT. Specifically, the gene expression of miR-451 was found to be 1,495 fold increase (p = 0.423) in group H compared to group S; In the N group, there was a 0.545 fold decrease (p=0,042) in the expression of the same genes according to the S group and we found 2,74 fold increase (p= 0,00262) between expression levels of mir-451 in H group compared to N group. These findings suggest that miR-451 is closely related to disease activity. HT is an autoimmune disease and its pathogenesis is still unknown. Many of the pathogenesis of the disease has been clarified and treatment alternatives are presented by introducing the important effects of miRNAs on the disease pathogenesis in recent years. The results of our study will lead to clarify HT pathogenesis in light and to develop new therapeutic approaches.
Author
Dr. Hale Önder Yılmaz
How to Cite
Hale Önder Yılmaz (Medical Specialty Thesis). The role of mikrornas in hashimoto thyroiditis, 2017, Karadeniz Technical University.
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