Search In this Thesis
   Search In this Thesis  
العنوان
Whole genome 5’-Methylcytosine Level quantification in chronic Hepatitis C infected Egyptian patients =
المؤلف
Deghady, Norhan Adel Mohamed.
هيئة الاعداد
باحث / نورهان عادل محمد دغيدي
مشرف / وفاء سعد رجب
مشرف / احمد مصطفى عوض
مناقش / منى وجدى عياد
مناقش / رانيا محمد الشرقاوى
الموضوع
Chemical Pathology.
تاريخ النشر
2017.
عدد الصفحات
94 p. :
اللغة
الإنجليزية
الدرجة
ماجستير
التخصص
علم الأمراض والطب الشرعي
تاريخ الإجازة
26/10/2017
مكان الإجازة
جامعة الاسكندريه - معهد البحوث الطبية - الباثولوجيا الكيميائية
الفهرس
Only 14 pages are availabe for public view

from 100

from 100

Abstract

DNA methylation is an epigenetic mechanism used by cells to control gene expression. A number of mechanisms exist to control gene expression in eukaryotes, but DNA methylation is a commonly used epigenetic signaling tool that can hold genes in the “off” position.CpG islands are generally found in close proximity to transcription start sites, suggesting there is an established recognition system.
DNA methylation changes with HCV viral infection are time dependent and progress slowly.
Chronic infection with hepatitis C virus (HCV) is considered a major risk for chronic liver impairment. It is the most common leading cause to HCC.
The present work aimed at studying whole genome 5 methyl cytosine levels in chronic hepatitis C infected Egyptian patients.
In present study 120 Egyptian adults were included. They were divided into two groups: group І (40 apparently healthy control subjects) and group ІІ (80 HCV infected patients from internal medicine department in medical research institute). group ІІ was further subdivided into two subgroups: group ІI a (60 HCV infected patients without HCC) and group ІІ b (20 HCV infected patients with HCC).
HCV patients were sub classified according to Child Pugh classes to assess the liver condition. To all studied subjects the level of 5-mc% was measured in peripheral blood using Methyl Flash TM Methylated DNA Quantification ELISA Kit.
In the present study, we did not find a significant correlation between age and 5- methyl cytosine (p=.356).To all studied subjects detailed history and complete clinical examination were done.
In the present study, the median of 5 Methylcytosine % in the control group (group I) was 2.5, in HCV group (group IIa) was 2.45 and in HCC group (group II b) was 2.25.A step wise decrease in 5- Methyl cytosine % from control (group I) toward HCC (group IIb) was observed, taking in consideration that the step wise global hypomethylation was not statistically significant. (p=.811).
In our study, there was more decrease in 5 methylcytosie% in HCV patient suffering from more deterioration in liver function and higher degree of liver cirrhosis. Asits 5 methylcytosine % levels were compared among the studied HCV patients after classifying themaccording to Child pugh grades , it was found that median of 5 methylcytosine% in Child Apatientswas (3.85%), in Child B patientswas (2.35%) and in Child Cpatients was (2.26%).(P=0.443)
It was found that there is a negative correlation between ALT and 5 methylcytosine% (p=-0.029). from these findings it could be speculated that more liver damage is associated with high ALT level and a decrease in global DNA methylation.
In the current study, we found by univaraitelogestic regression analysis that 5 –Methyl cytosine % is not a risk factor for liver cirrhosis development, as Odd׳s ratio was .967(.887-1.054) p=.442.Also 5 –Methyl cytosine % did not have statistical significant impact on the development of HCC where Odds ratio was 1.032(.892-1.194).In addition there was no correlation between 5 methylcytosine% and alpha fetoprotein.
from the present study the following could be concluded:
1- Global DNA 5mc% did not differ in HCV infected patients and HCC patients than normal controls, denoting that the chronic HCV inflammatory process itself could not influence the global DNA methylation status.
2- 5mc% was negatively correlated with ALT denoting a trend of decrease in 5mc% with more liver damage.
3-5 methylcytosine% had no impact on liver cirrhosis or HCC.
4-5mc% did not show any correlation between age, AFP, HCV viral load, and Child Pugh class in the studied subjects.