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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. |