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العنوان
Association Between Cyclin-Dependent Kinase Inhibitor 2B Antisense RNA 1 and Zinc Finger Homeobox 3 Gene Polymorphisms and COVID-19 Infection /
المؤلف
Nagy, Alaa Osama Zeid.
هيئة الاعداد
باحث / الاء اسامة زيد ناجي
مشرف / ايمان عبد الفتاح بدر
مشرف / نسرين جمال الدين الهلباوي
مشرف / شيرين صبحي النيداني
الموضوع
COVID-19 (Disease) Treatment . Biochemistry. Molecular biology.
تاريخ النشر
2024.
عدد الصفحات
147 p. :
اللغة
العربية
الدرجة
الدكتوراه
التخصص
الكيمياء الحيوية (الطبية)
تاريخ الإجازة
30/3/2024
مكان الإجازة
جامعة المنوفية - كلية الطب - الكيمياء الحيوية
الفهرس
يوجد فقط 14 صفحة متاحة للعرض العام

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المستخلص

The novel coronavirus related to beta coronaviruses was named SARSCoV-
2, and in March 2020, COVID-19 was declared a pandemic by WHO.
The health threats and economic burden caused by these CoVs are
extremely serious
There are variations in the degree of severity of COVID-19, ranging
from no symptoms and mild symptoms to IMCU admission to ICU
admission and mechanical ventilation.
SARS-CoV-2 patients with cardiovascular diseases are at risk of a
severe outcome compared with patients without such conditions.
Cyclins and CDKs are the main regulators of the progression of the cell
cycle. Many viruses, including CoV, facilitate viral replication by
regulating cell cycle progression through cyclin-CDK complexes.
CDKN2B-AS1 gene is located in the CDKN2B-CDKN2A gene cluster
of chromosome 9p21. It encodes lncRNA molecule that interacts with
PRC1 and PRC2, leading to epigenetic silencing of other genes in this
cluster. Previous studies have identified that proteins originating from this
gene cluster are highly expressed in atherosclerotic lesions and promote
vascular remodelling, thrombogenesis and plaque stability.
This study aimed to investigate whether there is an association between
CDKN2B-AS1 (rs1333049) and ZFHX3 (rs2106261) SNPs and the degree
of COVID-19 severity.
This case‒controlled study was carried out by cooperation between
Medical Biochemistry & Molecular Biology and Anesthesiology, Intensive
Care & Pain Management Departments, Faculty of Medicine, Menoufia
University. It included 180 subjects, 90 COVID-19 patients and 90 ageand
gender-matched healthy controls. The patients were recruited from ICU
Summary
107
and IMCU, Menoufia University Hospital. This study was carried out
between January 2022 and November 2022.
The studied subjects were classified into the following groups:
group Ia: 45 severe COVID-19 patients.
They were 17 males and 28 females. Their mean age X ± SD was 68.13
± 8.65 years.
group Ib: 45 moderate COVID-19 patients.
They were 24 males and 21 females. Their mean age X ± SD was 58.18
± 17.46 years.
group II: 90 apparently healthy age- and gender-matched controls.
They were 40 males and 50 females. Their mean age X ± SD was 63.22
± 11.16 years.
All studied subjects were subjected to the following:
1- Full history taking.
2- General clinical examination.
3- Radiological examination (chest X-ray and chest CT).
4- Laboratory investigations included CBC, liver function enzymes,
kidney function tests (BUN, creatinine, Na+ and K+), lipid profile, PC%,
INR, CRP, ferritin and D-dimer.
5- PCR nasopharyngeal swab to confirm the diagnosis of COVID-19.
6- Detection of CDKN2B-AS1 (rs1333049) and ZFHX3 (rs2106261)
SNPs by genotyping DNA extracted from whole blood samples using
the TaqMan allelic discrimination assay technique by RT‒PCR .
The results of the present study can be summarized as
follows:
 Regarding age, there is a significant difference between group Ia and
group Ib .
Summary
108
 Regarding vaccination, there is a significant difference between the
three studied groups with predominance in the control group.
 Regarding laboratory data, there is a significant increase in WBCs
count in both patients’ groups compared with controls. There is a
significant decrease in platelet count and HB concentration in both
patients’ groups compared with controls. Whereas there is a significant
decrease in HB concentration in group Ia compared with group Ib and a
significant increase in creatinine in group Ia compared with group Ib
and controls.There is a significant increase in SGOT, BUN, TG, INR,
CRP, ferritin and D-dimer in both patients’ groups when compared
with control group whereas there is a significant decrease in total
cholesterol, HDL, LDL and PC% in both patients’ groups on comparing
to control group. There is a significant increase in K+ level in group Ia
compared with controls.
 Regarding associated comorbidities and complications, There is a
significant increase in the frequency of MI, HTN and DM in group Ia
compared with group Ib, whereas there is no significant difference
regarding other associated comorbidities (old stroke and COPD). There
is a significant increase in ARDS and DCL in group Ia compared with
group Ib, while no significant difference is found regarding other
complications.
 Regarding prognosis, there is a significant increase in number of deaths
among group Ia compared with group Ib.
 There is a significant difference regarding the genotype frequency and
allelic distribution of CDKN2B-AS1 (rs1333049) between the three
studied groups. The frequency of the GC genotype is significantly
higher in group Ia and group Ib when compered to control group, while
the frequency of the CC genotype is significantly higher in group Ib
when compared to control group.
Summary
109
 Regarding CDKN2B-AS1 (rs1333049), a significantly higher
prevalence of the genotype (GC) and the variant allele (C) in the severe
COVID-19 group patients compared to the control group is observed
under the dominant, codominant-1, overdominant and log additive
modes of inheritance, and in the moderate COVID-19 group, patients
compared to the control group are observed under the dominant,
codominant-1 and log additive modes of inheritance. A significantly
higher prevalence of the CC genotype in the moderate COVID-19
group than in the control group is observed under the codominant-2
mode of inheritance.
 There is a significant decrease in WBCs and platelet count in severe
COVID-19 patients whereas there is a significant increase in ferritin
level in G/C and C/C genotypes compared to the G/G genotype.
 There is a significant decrease in platelet count in moderate COVID-19
patients in G/C and C/C genotypes compared to the G/G genotype
whereas there is a significant increase in INR in the G/C genotype.
 There is a significant association of lower TG and cholesterol levels in
dead COVID-19 patients.
 There is a significant association of older age, higher WBC count and
lower TG level (p=0.035) in dead COVID-19 patients.