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العنوان
Investigatingthe Possible Association
Between Gene Variant(s) and Progression of
Hepatocellular Carcinoma /
المؤلف
Abdeldayem, Nermin Abdeldayem Ali.
هيئة الاعداد
باحث / نرمين عبدالدايم علي عبدالدايم
مشرف / هالة عثمان المسلمى
مشرف / نادية حمدى الحنفى
مشرف / عبد الله احمد جبريل
تاريخ النشر
2021.
عدد الصفحات
121 P. :
اللغة
الإنجليزية
الدرجة
ماجستير
التخصص
الصيدلة ، علم السموم والصيدلانيات (المتنوعة)
تاريخ الإجازة
1/1/2021
مكان الإجازة
جامعة عين شمس - كلية الصيدلة - قسم الكيمياء الحيوية
الفهرس
Only 14 pages are availabe for public view

from 121

from 121

Abstract

Chronic hepatitis C is the one of most common causes of chronic viral liver disease worldwide, leading to significant morbidity and mortality, due to liver disease and HCC of infected persons.
Egypt has the highest incidence and prevalence of HCV infection worldwide. With more than 12 million infected individuals, CHC represents a major public health and economic burden in Egypt.
Unresolved chronic HCV infection could progress to more deteriorating conditions such as fibrosis, cirrhosis, and HCC.
Hepatocellular Carcinoma is considered the fifth most common cancer globally and the second leading cause for cancer related mortalities.
Recent genetic variants have emerged as genetic predispositions associated with HCC pathogenesis and progression.
The aim of this study was first, to screen the frequency of rs5742909, rs7574865 and rs2073498 SNPs in CTLA4, STAT4 and RASSF1A genes, respectively, in HCV-related-HCC in Egyptian patients. The second aim was to correlate the association of those SNPs with risk of HCC pathogenesis in Egypt.
In order to fulfil our aim, the present study was conducted on 150 subjects divided into the following three groups:
group (1): Healthy controls, fifty healthy volunteers (male=23, female=27, mean age=55.6 years, range 36-67 years).
group (2): HCV group, fifty patients (male=26, female=24, mean age=56.2 years, range 30-62 years).
group (3): HCV induced HCC, fifty patients (male=20, female=30, mean age=58.84 years, range 35-65 years).
All patients were recruited from the Outpatient Clinic of Health insurance and El Demrdash Hospitals, Cairo, Egypt. For healthy control samples were collected in the outpatient clinic at the British University in Egypt from healthy volunteers.
None of the healthy control volunteers were known to have a history of hepatic disorder and all of them had normal liver function tests and negative serological findings for viral liver diseases.
Full history and clinical data collection were obtained for each participant.
All patients were having HCV positive antigen and were genotype 4. Anti- HCV antibody assessment, viral load and genotyping were performed using real time PCR assay.
Exclusion criteria:
Patients with either one of the following conditions were excluded from the study, active co-infection with HBV, schistosomiasis, HIV, alcohol intake, thyroid dysfunction, inflammatory diseases, diabetes mellitus and cardiovascular disorders.
Additionally, in cases of HCC patients, they were excluded if they had started a chemotherapy regimen or had undergone a surgical operation.
The investigated variants were genotyped with PCR-Restriction Fragment Length Polymorphism (PCR-RFLP) technique.
Results of the current study can be summarized as follows:
1. The T mutant variant of rs2073498 SNP in RASSF1A exhibited positive correlation with HCC incidence risk (OR = 0.571, 95% CI = 0.175- 1.865, P<0.001) with more frequent T Allele distribution in HCV group and HCC group than in control group with statistical significance (22%, 20% and 8%, respectively) . The rs7574865 variant in STAT4 was highly frequent in both HCC and HCV groups with significant incidence risk with more frequent T Allele distribution in HCV group and HCC group than in control group with statistical significance (15%, 19% and 7%, respectively) (OR= 1.583, 95% CI = 1.123- 2.232, P<0.005). On the contrary, the rs5742909 change in CTLA4 did not show significant difference between HCV related HCC cases and control group (OR = 4.5, 95% CI = 1.326- 15.277, P=0.345), and the T Allele distribution of the rs5742909 SNP in CTLA4 gene in HCV and HCC groups showed comparable frequency as in control group(9%, 13% and 10%, respectively).
2. The following SNPs: rs2073498 (RASSF1A) and rs7574865 (STAT4) were found to have LD (D’=0.5) in Egyptian population. Extent of LD is lower between rs5742909 (CTLA4) and rs7574865 (STAT4) SNPs pair, and between rs2073498 (RASSF1A) and rs5742909 (CTLA4) SNPs pair (D’>1).
In Conclusion:
1. We report in this study, for the first time, positive correlation and association of rs2073498 (RASSF1A) and rs7574865 (STAT4) variants with incidence and progression of HCV G4-related HCC in Egyptian patients.
2. On the contrary, the rs5742909 change in CTLA4 gene among Egyptian patients revealed negative association with HCC progression arising from HCV G4.
3. Per the haplotype-block model of LD, within the study population, both rs2073498 (RASSF1A) and rs7574865 (STAT4) genes were found to be associated with disease susceptibility.
Therefore, rs2073498 (RASSF1A) and rs7574865 (STAT4) SNPs could be utilized as genetic susceptibility factors for HCV G4-mediated stimulant for HCC in Egyptian population.
1. Per the current study major finding that [rs2073498 (RASSF1A) and rs7574865 (STAT4) SNPs could be utilized as genetic susceptibility factors for HCV G4-mediated stimulant for HCC in Egyptian population], therefore, targeting the downstream proteins of these genes might be a new therapeutic approach.
2. Crosstalk between the molecular mechanisms suppressing HCV progression to HCC [like autophagy or microRNA] and the studied SNPs or genes, would be an emerging area of research.
3. The positive associations reported in our study for rs2073498 and rs7574865 SNPs in RASSF1A and STAT4 genes in G4 HCV mediated HCC Egyptian patients should be scaled up globally in other patients infected with different viral genotypes.
4. More formally, statistical power is the probability of finding a statistically significant result. A larger sample size should hypothetically lead to more accurate or representative results especially when it comes to surveying large populations.