Hashemi, Fatemeh

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        اﻓﻀﻠﯽ ﭘﻮر ﭘﺰﺷﮑﯽ داﻧﺸﮑﺪه  اﻧﺴﺎﻧﯽ ژﻧﺘﯿﮏ رﺷﺘﻪ ارﺷﺪ ﮐﺎرﺷﻨﺎﺳﯽ ﻣﻘﻄﻊ ﻧﺎﻣﻪ ﭘﺎﯾﺎن    ﻋﻨﻮان  ﮐﺮوﻧﺮی ﻋﺮوق ﺑﯿﻤﺎری ﺑﻪ ﻣﺒﺘﻼ اﻓﺮاد در ١ﺳﯿﺮﺗﻮﺋﯿﻦ ژن ﭘﺮوﻣﻮﺗﻮر ﻣﺘﯿﻼﺳﯿﻮن ﺑﺮرﺳﯽ      ﺗﻮﺳﻂ  هﺎﺷﻤﯽ ﻓﺎﻃﻤﻪ  راهﻨﻤﺎ اﺳﺎﺗﯿﺪ  ﮔﻮهﺮی ﺻﺎﻟﺢ ﻧﺼﺮاﻟﻠﻪ دﮐﺘﺮﺳﻌﯿﺪی ﮐﻠﺜﻮم دﮐﺘﺮ  (٨٩ﺷﻬﺮﯾﻮر) ﺗﺤﺼﯿﻠﯽ ﺳﺎل                                                                              ۴۴۵ﻧﺎﻣﻪ:ﺷﻤﺎره ﭘﺎﯾﺎن       ﭼﮑﯿﺪه. ﮔﺰارﺷـﺎت ﺑﺎﺷـﺪﯽدر ﺳﺮاﺳـﺮ ﺟﻬـﺎن ﻣـ ﯿﺮاز ﻋﻮاﻣﻞ ﻋﻤﺪه ﻣﺮگ و ﻣ ﯾﮑﯽ یﻋﺮوق ﮐﺮوﻧﺮ ﯿﻤﺎریﺑ :و اهﺪاف ﻣﻘﺪﻣﻪﻋﻮاﻣﻞ  ﯿﻦﺑﻮده ﮐﻪ ﺑ ﯾﺲآﺗﺮواﺳﮑﻠﺮوز اﯾﺠﺎددر  ﯿﺮاز ﻋﻮاﻣﻞ ﻣﻬﻢ درﮔ ﯾﮑﯽ، AND ﯿﻼﺳﯿﻮناز آن اﺳﺖ ﮐﻪ ﻣﺘ ﯽﺣﺎﮐﻟﻮﮐـﻮس  ﯾﻦ، ﭼﻨﺪANDﺘﯿﻼﺳﯿﻮنﺑﺎ ﻣﻄﺎﻟﻌﻪ ﻣ ﯾﯽهﺎ. ﭘﮋوهﺶﮐﻨﺪﯽارﺗﺒﺎط ﺑﺮﻗﺮار ﻣ ﯿﻤﺎریﺑ ﯾﻦا ﯿﮑﯽو ژﻧﺘ ﯿﻄﯽﻣﺤﻧﺸﺎن داده اﺳـﺖ  ﯿﻘﺎتاﻧﺪ. ﺗﺤﻘداده ﯿﺸﻨﻬﺎدﭘ ﯿﻤﺎریﺑ ﯾﻦا ﯿﺸﺮﻓﺖﮐﻨﻨﺪه، ﺷﺮوع و ﭘ ﺑﯿﻨﯽﯿﺶرا ﺑﻪ ﻋﻨﻮان ﻋﻮاﻣﻞ ﭘ ﯿﺎلاﻧـﺪوﺗﻠ ،ﯿﺖﻣﻮﻧﻮﺳـ یهـﺎﻣـﺮﺗﺒﻂ در ﺳـﻠﻮل ﯽو ﻣﺮگ ﺳﻠﻮﻟ یآﺗﻮﻓﺎژ ﯿﺪاﺗﯿﻮ،اﺳﺘﺮس اﮐﺴ ﯽ،اﻟﺘﻬﺎﺑ ﯿﺮهﺎیﮐﻪ ﻣﺴ. ﺑﺎﺷـﻨﺪﯽﻣـ ﯿﻤـﺎریﺑ ﯾـﻦدر ا ﯿـﺮدرﮔ ﯽاﺻﻠ ﯿﺮهﺎی، از ﻣﺴ)sCMSV(ﯽﻋﺮوﻗ یا ﯿﭽﻪﺻﺎف ﻣﺎه یهﺎﺳﻠﻮل ﻋﺮوق و یهـﺎﻧﻘـﺶ ﯿﺮهﺎ،ﻣﺴـ ﯾـﻦدر ا ﯽﻋﻨﺼـﺮ اﺻـﻠ ﯾﻦﭼﻨﺪ ﯿﺎنﺑ ﯿﻢاﺳﺖ ﺑﺎ ﺗﻨﻈ ﯿﻼزداﺳﺘ ﯿﺴﺘﻮنه ﯾﮏﮐﻪ  ﯿﺮﺗﻮﺋﯿﻦژن ﺳدر ﺣﻔﺎﻇـﺖ از  ﯿـﺪیﻋﺎﻣـﻞ ﻣﻬـﻢ و ﮐﻠ ﯾـﻦﮐـﺮده و ﺑﻨـﺎﺑﺮ ا ﯾﻔـﺎرا ا ﻏﯿـﺮه و ﯽو ﺿـﺪاﻟﺘﻬﺎﺑ ﯿﺪاﻧﯽاﮐﺴ ﯽآﻧﺘ ﯿﺮی،ﺿﺪ ﭘ ﺗﻮاﻧـﺪﯽﻣـ ﺷـﻮﻧﺪﯽژن ﻣـ ﯾـﻦا ﯿﺎنﺑ ﯿﻢﮐﻪ ﺳﺒﺐ ﺗﻨﻈ ﯽﮐﺮدن ﻋﻮاﻣﻠ ﯿﺪاﭘ ﯿﺠﻪ. در ﻧﺘﺑﺎﺷﺪﯽﻣ ﯽﻋﺮوﻗ -ﯽﻗﻠﺒ ﯿﺴﺘﻢﺳ ﯽﻣﻄﺎﻟﻌـﻪ ﺑﺮرﺳـ ﯾـﻦﺷـﻮد. هـﺪف از ا ﯿﻤـﺎریرا ﻣﺸـﺨﺺ ﮐﻨـﺪ و ﺳـﺒﺐ ﺑﻬﺒـﻮد ﺑ ﯾـﺪﺟﺪ یﺧﺖ داروهـﺎﺳـﺎ ﯿﺮﻣﺴـ  .ﺑﺎﺷﺪﻣﯽ ﺳﺎﻟﻢ اﻓﺮاد و یﻋﺮوق ﮐﺮوﻧﺮ ﯿﻤﺎریدر اﻓﺮاد ﻣﺒﺘﻼ ﺑﻪ ﺑ ﯿﺮﺗﻮﺋﯿﻦﭘﺮوﻣﻮﺗﻮر ژن ﺳ ﯿﻼﺳﯿﻮنﻣﺘﻧﻔﺮ  ٨٢ﮐﻪ  ﻧﻔﺮ را ﺑﺮ اﺳﺎس ﻣﻌﯿﺎرهﺎی ﺧﺎﺻﯽ اﻧﺘﺨﺎب ﮐﺮده٠٩از ﺑﯿﻦ اﻓﺮادی ﮐﻪ آﻧﮋﯾﻮﮔﺮاﻓﯽ ﺷﺪه ﺑﻮدﻧﺪ،  :هﺎروشﺑـﻪ  ﯽﺧـﻮﻧ هـﺎیﯿﺖاﻓـﺮاد، ﻣﻮﻧﻮﺳـ ﯾـﻦا ﯽﻣﺒﺘﻼ ﺑﻮدﻧﺪ. از ﻧﻤﻮﻧـﻪ ﺧـﻮﻧ ﯿﻤﺎریﺑ ﯾﻦهﺎ ﺑﻪ اﻧﻔﺮ آن ٢۶هﺎ ﻧﺮﻣﺎل و از آن-SMﯿـﮏاز ﺗﮑﻨ ﯾـﺖو در ﻧﻬﺎ ﯾـﺪﮔﺮد ﯿﺘﻪﺳـﻮﻟﻔﯽﺑـ و هﺎ اﺳﺘﺨﺮاج ﺷﺪآن ANDﺟﺪا ﺷﺪه و  SCAM ﯿﮏﮐﻤﮏ ﺗﮑﻨ  اﺳﺘﻔﺎده ﺷﺪ. ﯿﻼﺳﯿﻮنﻣﺘ ﯽﺟﻬﺖ ﺑﺮرﺳ MRH tset-t tnednepedni: ارﺗﺒﺎط ﺑﯿﻦ ﻣﺘﯿﻼﺳﯿﻮن ﭘﺮوﻣﻮﺗﻮر ژن ﺳﯿﺮﺗﻮﺋﯿﻦ و ﺑﯿﻤﺎری ﻋﺮوق ﮐﺮوﻧﺮی ﺑـﺎ آزﻣـﻮن ﯾﺎﻓﺘﻪ هﺎ  ﻧﺸﺎن داد ﮐﻪ ﺑﯿﻦ آن دو ارﺗﺒﺎﻃﯽ وﺟﻮد ﻧﺪارد. ٩٩٧٫٠=eulaV-P. ﺑﺮرﺳﯽ ﺷﺪﯾﮑﯽ از ﻋﻮاﻣﻞ اﯾﺠـﺎد و ﯾـﺎ ﭘﯿﺸـﺮﻓﺖ ﺑﯿﻤـﺎری  ANDاﻧﺪ ﮐﻪ ﻣﺘﯿﻼﺳﯿﻮن ﻣﻄﺎﻟﻌﺎت ﻧﺸﺎن داده :ﯿﺮیﮔ ﻧﺘﯿﺠﻪﺑﺤﺚ و هﺎی درﮔﯿﺮ در اﯾﻦ ﺑﯿﻤﺎری اﺳﺖ ﮐـﻪ ﯾﮑـﯽ از ﻋﻮاﻣـﻞ ﯾﮑﯽ از ﻣﻬﻤﺘﺮﯾﻦ ژن ١ﺑﺎﺷﺪ.ژن ﺳﯿﺮﺗﻮﺋﯿﻦﻋﺮوق ﮐﺮوﻧﺮی ﻣﯽ ﯿﻼﺳـﯿﻮنﮐـﻪ ﻣﺘ رﺳـﺪﯽﺑﻪ ﻧﻈﺮ ﻣ ﺑﺎﺷﺪ.ﻃﺒﻖ آزﻣﺎﯾﺸﺎت ﻣﺎ،ﮐﻨﺘﺮل ﮐﻨﻨﺪه ﺑﯿﺎن آن ﻣﺘﯿﻼﺳﯿﻮن ﭘﺮوﻣﻮﺗﻮر اﯾﻦ ژن ﻣﯽ ژن ﻣﺬﮐﻮر ﺗﻮﺳـﻂ ﻋﻮاﻣـﻞ  ﯿﻤﺎریﺑ ﯾﻦدر ا ﺷﺎﯾﺪﻧﺪاﺷﺘﻪ ﺑﺎﺷﺪ و  یﻋﺮوق ﮐﺮوﻧﺮ ﯿﻤﺎریﺑﺎ ﺑ یژن، ارﺗﺒﺎط ﻣﻌﻨﺎدار ﯾﻦا   .ﺷﻮدﯽﻣ ﯿﻢﺗﻨﻈ هﺎANRاز ﺟﻤﻠﻪ ﻣﯿﮑﺮو  ﯾﮕﺮید MRH-SMژﻧﺘﯿﮏ، ﺑﯿﻤﺎری ﻋﺮوق ﮐﺮوﻧﺮی، آﺗﺮواﺳﮑﻠﺮوزﯾﺲ، ، ﻣﺘﯿﻼﺳﯿﻮن، اﭘﯽ١ﺳﯿﺮﺗﻮﺋﯿﻦ ﮐﻠﻤﺎت ﮐﻠﯿﺪی:                    Abstract Background and Objectives Coronary artery disease is one of the major causes of mortality worldwide. Reports indicate that DNA methylation is one of the important factors involved in the pathogenesis of atherosclerosis, which links environmental and genetic factors. Some Studies on DNA methylation have suggested that several loci(DMR) are as predictors, initiation and progression of the disease. Researches have shown that inflammatory pathways, oxidative stress, autophagy, and programmed cell death in monocytes, endothelial cells(ECs) and vascular smooth muscle cells (VSMCs) are major pathways involved in this disease. The Sirtuin1 gene, a histone deacetylase, plays an anti-aging, antioxidant and anti-inflammatory role by regulating the expression of several key elements in these pathways and is therefore an important factor in protecting the cardiovascular system. As a result, finding the factors that regulate the expression of this gene can determine new strategies for the development of novel drugs and improve the disease. We measured the promoter methylation of Sirtuin1 in people with coronary artery disease and healthy people. Methods: 62 CAD patients and 28 normal control are selected according to specific criteria. From the blood samples of these individuals, blood monocytes were isolated by MACS technique and their DNA were extracted and was bisulfited. finally the MS-HRM technique was used in order to analyze the DNA methylatin. Results: The association between sirtuin1 promoter methylation and coronary artery disease was assessed by independent t-test. P-Value = 0.799 showed no relationship between the two. Discussion and Conclusion: Studies have shown that DNA methylation is a factor in the development or progression of coronary artery disease. Sirtoin 1 gene is one of the most important genes involved in this disease and one of the controlling factors of its expression is promoter methylation of this gene. According to our results, methylation of this gene did not not appear to be significantly correlated with coronary artery disease, and this gene may be regulated by other factors, such as microRNAs. Key words: SIRT1, Methylation, Epigenetics, coronary artery disease, Atherosclerosis, MS-HRM          Faculty of Medicine In Partial Fulfillment of the Requirements for the Degree(MSc)  Title Evaluation of sirtutin1 promoter methylation of patients with coronary artery disease  By Fatemeh Hashemi Supervisors Dr Kolsoum SaeidiDr Nasrollah Saleh gohari Thesis No: 544                                                                               Date:(September,2019)            

=Evaluation of sirtutin1 promoter methylation of patients with coronary artery disease

http://eprints.kmu.ac.ir/32079/1/7506.pdf

=Evaluation of sirtutin1 promoter methylation of patients with coronary artery disease

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