The Correlation of Single Nucleotide Polymorphism of the ACE2 rs4646116 Gene with The Severity of COVID-19

SUMMARY. Different genetic and immunological factors can affect the severity of Coronavirus disease 19. Angiotensin-converting enzyme 2 is a human receptor for Severe Acute Respiratory Syndrome Coro-navirus-2, and the successful interaction between the spike protein of the novel virus and Angiotensin-converting enzyme 2 is responsible for the initial and complete infection. The study aimed to evaluate the correlation between Single Nucleotide Polymorphisms of Angiotensin converting-enzyme 2, with disease severity of Coronavirus disease 19 in AL-Najaf province. The allele Specific-polymerase Chain reaction method was used for investigating Single Nucleotide polymorphisms of Angiotensin converting-enzyme 2 rs4646116 A/G in different states of Coronavirus disease 19 (COVID-19). The wild genotypes (GG) for ACE2 rs4646116 gene recorded a highly significant association p = 0.0009, and a high ratio in the control group (90%) in comparison with moderate cases of COVID-19 (60%). While the heterozygote genotype (GA) of the same gene showed a significant (p-value = 0.0144) and high ratio in moderate cases (30%) in comparison with the control group (10%). Conclusion(s): the wild genotype (GG) for Angiotensin convert-ing-enzyme 2 rs4646116 gene may be associated with more protection from infection with COVID-19. While the polymorphism heterozygote genotype (GA) for the same gene may be associated with more susceptibility to infection with COVID-19.Copyright © 2023, Colegio de Farmaceuticos de la Provincia de Buenos Aires. All rights reserved.

Polymorphisms in the inter leukin-1 beta gene (rs16944 and rs1143627) as a risk factor for SARS-COV2 infection

Despite evidence of cytokine gene variation in SARS-CoV-2 sickness is few, understanding the function of genetic polymorphisms in the course of respiratory infections may aid in the identification of possible andidates for future inquiry in SARS-CoV-2 patients. As a result, the study raises crucial issues about how cytokine gene polymorphisms may have a role in the severity of COVID-19 sickness. ARMS-PCR was used to detect genotype frequency data for the IL-1B SNP (rs 16944), (rs1143627). All data statistical analyses were performed using the Statistical Package for Social Science (SPSS 26).. shows the genotype distributions (frequencies) of the chosen IL-1B SNPs, rs16944 A/G and rs1143627 G/A, as well as their relationships with SARS-COV2 risk. Significant relationships between the rs16944 A/G and SARS-COV2 risk were found in the samples, The AG variant genotype (AG vs. AA) showed an adjusted OR of 1.0 (95 percent CI = 1.770 (0.935-0.353), P = 0.078*) when compared to the rs16944 AA genotype. There were no statistical differences in rs1143627 polymorphism between the two groups, and there was no evidence that rs1143627 may be associated with an increased risk of acquiring SARS-COV2 based on the results of the p value G (P = 0.167), G/A (P = 0.22), and G/G (P = 0.22). This was the first study to look at the rs1143627 polymorphism in relation to SARS-COV 2, therefore no previous research was published.first, second, and third level headings (first level heading). © 2023 Author(s).

In Silico Prediction and Molecular Docking of SNPs in NRP1 Gene Associated with SARS-COV-2.

Neuropilin-1 (NRP1) which is a main transmembrane cell surface receptor acts as a host cell mediator resulting in increasing the SARS-Cov-2 infectivity and also plays a role in neuronal development, angiogenesis and axonal outgrowth. The goal of this study is to estimate the impact of single nucleotide polymorphisms (SNPs) in the NRP1 gene on the function, structure and stabilization of protein as well as on the miRNA-mRNA binding regions using bioinformatical tools. It is also aimed to investigate the changes caused by SNPs in NRP1 on interactions with drug molecule and spike protein. The missense type of SNPs was analyzed using SIFT, PolyPhen-2, SNAP2, PROVEAN, Mutation Assessor, SNPs&GO, PhD-SNP, I-Mutant 3.0, MUpro, STRING, Project HOPE, ConSurf, and PolymiRTS. Docking analyses were conducted by AutoDock Vina program. As a result, a total of 733 missense SNPs were determined within the NRP1 gene and nine SNPs were specified as damaging to the protein. The modelling results showed that wild and mutant type amino acids had some different properties such as size, charge, and hydrophobicity. Additionally, their three-dimensional structures of protein were utilized for confirmation of these differences. After evaluating the results, nine polymorphisms rs141633354, rs142121081, rs145954532, rs200028992, rs200660300, rs369312020, rs370117610, rs370551432, rs370641686 were determined to be damaging on the structure and function of NRP1 protein and located in conserved regions. The results of molecular docking showed that the binding affinity values are nearly the same for wild-type and mutant structures support that the mutations carried out are not in the focus of the binding site, therefore the ligand does not affect the binding energy. It is expected that the results will be useful for future studies.

Candidate SNP Markers Significantly Altering the Affinity of TATA-Binding Protein for the Promoters of Human Hub Genes for Atherogenesis, Atherosclerosis and Atheroprotection.

Atherosclerosis is a systemic disease in which focal lesions in arteries promote the build-up of lipoproteins and cholesterol they are transporting. The development of atheroma (atherogenesis) narrows blood vessels, reduces the blood supply and leads to cardiovascular diseases. According to the World Health Organization (WHO), cardiovascular diseases are the leading cause of death, which has been especially boosted since the COVID-19 pandemic. There is a variety of contributors to atherosclerosis, including lifestyle factors and genetic predisposition. Antioxidant diets and recreational exercises act as atheroprotectors and can retard atherogenesis. The search for molecular markers of atherogenesis and atheroprotection for predictive, preventive and personalized medicine appears to be the most promising direction for the study of atherosclerosis. In this work, we have analyzed 1068 human genes associated with atherogenesis, atherosclerosis and atheroprotection. The hub genes regulating these processes have been found to be the most ancient. In silico analysis of all 5112 SNPs in their promoters has revealed 330 candidate SNP markers, which statistically significantly change the affinity of the TATA-binding protein (TBP) for these promoters. These molecular markers have made us confident that natural selection acts against underexpression of the hub genes for atherogenesis, atherosclerosis and atheroprotection. At the same time, upregulation of the one for atheroprotection promotes human health.

Genetic Variants within SARS-CoV-2 Human Receptor Genes May Contribute to Variable Disease Outcomes in Different Ethnicities.

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has evolved into a global pandemic, with an alarming infectivity and mortality rate. Studies have examined genetic effects on SARS-CoV-2 disease susceptibility and severity within Eurasian populations. These studies identified contrasting effects on the severity of disease between African populations. Genetic factors can explain some of the diversity observed within SARS-CoV-2 disease susceptibility and severity. Single nucleotide polymorphisms (SNPs) within the SARS-CoV-2 receptor genes have demonstrated detrimental and protective effects across ethnic groups. For example, the TT genotype of rs2285666 (Angiotensin-converting enzyme 2 (ACE2)) is associated with the severity of SARS-CoV-2 disease, which is found at higher frequency within Asian individuals compared to African and European individuals. In this study, we examined four SARS-CoV-2 receptors, ACE2, Transmembrane serine protease 2 (TMPRSS2), Neuropilin-1 (NRP1), and Basigin (CD147). A total of 42 SNPs located within the four receptors were reviewed: ACE2 (12), TMPRSS2 (10), BSG (CD147) (5), and NRP1 (15). These SNPs may be determining factors for the decreased disease severity observed within African individuals. Furthermore, we highlight the absence of genetic studies within the African population and emphasize the importance of further research. This review provides a comprehensive summary of specific variants within the SARS-CoV-2 receptor genes, which can offer a better understanding of the pathology of the SARS-CoV-2 pandemic and identify novel potential therapeutic targets.

Development and authentication of Panax ginseng cv. Sunhong with high yield and multiple tolerance to heat damage, rusty roots and lodging.

Ginseng (Panax ginseng) has been used as a valuable medicinal plant in Asia, and the demand for ginseng production for health functional food is increasing worldwide after the COVID-19 crisis. Although a number of cultivars have been developed to increase ginseng production, none of them were widely cultivated in Korea because they could not resist various environmental stresses while being grown in one place for at least 4 years. To address this, Sunhong was developed as a ginseng cultivar with high yield and multiple stress tolerance by pure line selection. Sunhong showed high yield and heat tolerance comparable to Yunpoong, a representative high-yielding cultivar, and exhibited 1.4 times lower prevalence of rusty roots than Yunpoong, suggesting that Sunhong can keep its high yield and quality during long-term cultivation. In addition, distinct color and lodging resistance were expected to increase the convenience of cultivation. To supply pure seeds to farmers, we also established a reliable high-throughput authentication system for Sunhong and seven ginseng cultivars through genotyping-by-sequencing (GBS) analysis. The GBS approach enabled to identify a sufficient number of informative SNPs in ginseng, a heterozygous and polyploid species. These results contribute to the improvement of yield, quality, and homogeneity, and therefore promote the ginseng industry. Supplementary Information: The online version contains supplementary material available at 10.1007/s13580-023-00526-x.

Pilot genome-wide association study of antibody response to inactivated SARS-CoV-2 vaccines.

Vaccines are a key weapon against the COVID-19 pandemic caused by SARS-CoV-2. However, there are inter-individual differences in immune response to SARS-CoV-2 vaccines and genetic contributions to these differences have barely been investigated. Here, we performed genome-wide association study (GWAS) of antibody levels in 168 inactivated SARS-CoV-2 vaccine recipients. A total of 177 SNPs, corresponding to 41 independent loci, were identified to be associated with IgG, total antibodies or neutral antibodies. Specifically, the rs4543780, the intronic variant of FAM89A gene, was associated with total antibodies level and was annotated as a potential regulatory variant affecting gene expression of FAM89A, a biomarker differentiating bacterial from viral infections in febrile children. These findings might advance our knowledge of the molecular mechanisms driving immunity to SARS-CoV-2 vaccine.

Detection of SARS-CoV-2 Variants via Different Diagnostics Assays Based on Single-Nucleotide Polymorphism Analysis.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is characterized by fast evolution with the appearance of several variants. Next-Generation Sequencing (NGS) technology is considered the gold standard for monitoring known and new SARS-CoV-2 variants. However, the complexity of this technology renders this approach impracticable in laboratories located in areas with limited resources. We analyzed the capability of the ThermoFisher TaqPath COVID-19 RT-PCR (TaqPath) and the Seegene Novaplex SARS-CoV-2 Variant assay (Novaplex) to detect Omicron variants; the Allplex VariantII (Allplex) was also evaluated for Delta variants. Sanger sequencing (SaS) was the reference method. The results obtained with n = 355 nasopharyngeal samples were: negative with TaqPath, although positive with other qualitative molecular assays (n = 35); undetermined (n = 40) with both the assays; negative for the ∆69/70 mutation and confirmed as the Delta variant via SaS (n = 100); positive for ∆69/70 and confirmed as Omicron BA.1 via SaS (n = 80); negative for ∆69/70 and typed as Omicron BA.2 via SaS (n = 80). Novaplex typed 27.5% of samples as undetermined with TaqPath, 11.4% of samples as negative with TaqPath, and confirmed 100% of samples were Omicron subtypes. In total, 99/100 samples were confirmed as the Delta variant with Allplex with a positive per cent agreement (PPA) of 98% compared to SaS. As undermined samples with Novaplex showed RdRp median Ct values (Ct = 35.4) statistically higher than those of typed samples (median Ct value = 22.0; p < 0.0001, Mann-Whitney test), the inability to establish SARS-CoV-2 variants was probably linked to the low viral load. No amplification was obtained with SaS among all 35 negative TaqPath samples. Overall, 20% of samples which were typed as negative or undetermined with TaqPath, and among them, twelve were not typed even by SaS, but they were instead correctly identified with Novaplex. Although full-genome sequencing remains the elected method to characterize new strains, our data show the high ability of a SNP-based assay to identify VOCs, also resolving samples typed as undetermined with TaqPath.

The Rs17713054 and Rs1800629 Polymorphisms of Genes Lztfl1 and Tnfare Associated with Covid-19 Severity

Both genetic and non-genetic factors are responsible for high interindividual variability in response to SARS-CoV-2. Despite the fact that multiple genetic polymorphisms have been identified as risk factors of severe COVID-19, such polymorphisms are still insufficiently studied in the Russian population. The study was aimed to identify genetic determinants associated with severe COVID-19 in the sample of patients from the Russian Federation. The correlation of the rs17713054 polymorphism in gene LZTFL1 and rs1800629 polymorphism in gene TNF (tumor necrosis factor) with the COVID-19 severity was assessed. DNA samples obtained from 713 patients (324 males and 389 females) aged 18-95 with COVID-19 of varying severity were analyzed. The rs1800629 polymorphism of gene TNF (OR = 1.5;p = 0.02) and rs17713054 polymorphism of gene LZTFL1 (OR = 1.60;p = 0.0043) were identified as risk factors of severe disease. The TNF polymorphism rs1800629 and LZTFL1 polymorphism rs17713054 could be considered as potential predictive biomarkers. The rs17713054 G > A polymorphism was strongly associated with severe disease. In the future the findings may provide the basis for the development of test-systems for prediction of the risk of severe viral respiratory diseases.

Genetic polymorphism between the Sorani and Hawrami kurdish populations and COVID-19 outcome.

BACKGROUND: Coronavirus Disease 2019 (COVID-19) is a global pandemic, and mortality and clinical consequences vary across countries. One of the factors influencing COVID-19 outcomes is genetic polymorphism. Two Kurdish populations, Sorani and Hawrami, live in the Sulaimani province of the Kurdistan Region of Iraq. It seems Hawrami had a milder COVID-19 outcome. According to previous research conducted on various ethnic groups across the globe, single nucleotide polymorphisms (SNPs) in the interferon-induced transmembrane protein 3 (IFITM3) and interluken-6 (IL6) genes were associated with the severity of COVID-19 in those populations. METHODS AND RESULTS: We hypothesized that Hawrami may have protective SNPs. So, in this study, we used DNA sequencing to genotype three IFITM3 SNPs and nine IL6 SNPs by DNA sequencing to investigate the association of Sorani and Hawrami population polymorphisms. Genotype AA for the rs12252 SNP in IFITM3 was insignificantly more common in the Sorani group (54% vs. 44%). The Hawrami population showed a higher percentage of the CC genotype of the rs34481144 SNP in the IFITM3 gene (62% vs. 44.3%) and a higher proportion of the non-risky GG genotype of the rs1800795 SNP in the IL6 gene (53.4 vs. 43.3); however, the SNPs were insignificantly associated between the two populations. CONCLUSIONS: IFITM3 and IL6 SNPs have no statistically significant association between the two Kurdish populations. The decreased proportion of non-risk alleles at rs34481144 and rs1800795 in the Hawrami population may partially support the research hypothesis. However, contrary to our hypothesis, the Sorani group had an insignificantly higher protective variant of the rs12252 SNP.

Human variation in the protein receptor ACE2 affects its binding affinity to SARS-CoV-2 in a variant-dependent manner.

SARS-CoV-2 infection depend on the binding of the viral Spike glycoprotein (S) to the human receptor Angiotensin Converting Enzyme 2 (ACE2) to induce virus-cell membrane fusion. S protein evolved diverse amino acid changes that are possibly linked to more efficient binding to human ACE2, which might explain part of the increase in frequency of SARS-CoV-2 Variants Of Concern (VOCs). In this work, we investigated the role of ACE2 protein variations that are naturally found in human populations and its binding affinity with S protein from SARS-CoV-2 representative genotypes, based on a series of in silico approaches involving molecular modelling, docking and molecular dynamics simulations. Our results indicate that SARS-CoV-2 VOCs bind more efficiently to the human receptor ACE2 than the ancestral Wuhan genotype. Additionally, variations in the ACE2 protein can affect SARS-CoV-2 binding and protein-protein stability, mostly making the interaction weaker and unstable in some cases. We show that some VOCs, such as B.1.1.7 and P.1 are much less sensitive to ACE2 variants, while others like B.1.351 appear to be specifically optimized to bind to the widespread wild-type ACE2 protein.Communicated by Ramaswamy H. Sarma.

Genomic characterization and phylogenetic analysis of sars-cov-2 in libya

The COVID-19 epidemic started in Libya in March 2020 and rapidly spread. To shed some light on the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) strains circulating in Libya, viruses isolated from 10 patients in this country were sequenced, characterized at the genomic level, and compared to genomes isolated in other parts of the world. As nine genomes out of 10 belonged to the SS1 cluster and one to SS4, three datasets were built. One included only African strains and the other two contained internationally representative SS1 and SS4 genomes. Genomic analysis showed that the Libyan strains have some peculiar features in addition to those reported in other world regions. Considering the countries in which the strains are genetically more similar to the Libyan strains, SARS-CoV-2 could have entered Libya from a North African country (possibly Egypt), sub-Saharan Africa (e.g., Ghana, Mali, Nigeria), the Middle East (e.g., Saudi Arabia), or Asia (India, Bangladesh).Copyright © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Analysis of Mutations in Conserved and Susceptible Regions Across the Whole Genome Sequencing Analysis for SARS-CoV-2 in Iraqi Patients

This study aimed to get a better understanding of molecular epidemiology and genetic variation in the spike glycoprotein as a key viral component involved in viral entrance into host cells and as a potential vaccination target. Three Iraqi SARSCoV- 2 strains were investigated using whole-genome sequencing, with two of them clustering into the 20A (GH) clade, and the remaining strain is clustered in 20E (GV) clade, belonging to the B.1.36.1 and B.1.177.80 lineage, respectively. Wholegenome sequencing of the viral RNA samples revealed nine sporadic nonsynonymous uncommon mutations with frequency ranged from 0.00 to 0.19%. The ORF1ab, ORF1a, ORF3a, S, N, intergenic, ORF7 and ORF8 areas have seen the most changes. Furthermore, in all of our sequences, we discovered a D614G (aspartic acid to glycine) mutation in spike protein that co-occurred with an NSP12 P323L (viral RNA-dependent RNA polymerase) mutation. The findings point to several viral introductions in Iraq and provide new genetic information on SARSCoV- 2 at the worldwide level. Pathogenesis, diagnostics and vaccine development require information such as SNPs and mutations. © 2023 Publishing house Mining book. All rights reserved.

ACE2 enhance viral infection or viral infection aggravate the underlying diseases.

ACE2 plays a critical role in SARS-CoV-2 infection to cause COVID-19 and SARS-CoV-2 spike protein binds to ACE2 and probably functionally inhibits ACE2 to aggravate the underlying diseases of COVID-19. The important factors that affect the severity and fatality of COVID-19 include patients' underlying diseases and ages. Therefore, particular care to the patients with underlying diseases is needed during the treatment of COVID-19 patients.

TYK2 single-nucleotide variants associated with the severity of COVID-19 disease.

Coronavirus disease 2019 (COVID-19) is a lethal disease caused by the coronavirus SARS-CoV-2, which can result in a broad clinical spectrum of respiratory symptoms. While many clinical risk factors such as concomitant chronic diseases play roles in the pathophysiology of COVID-19, genetic predisposition factors have not been widely studied. The aim of this study was, therefore, to evaluate the relationship between some singlenucleotide polymorphisms (SNPs) of the human genes TYK2 and ACE2 and the severity of SARS-CoV-2 infection. Genomic DNA was isolated from 200 SARS-CoV-2-infected individuals with severe (n = 100) or mild (n = 100) disease. Owing to the importance of ACE2 and TYK2 genes in regulating the immune response to SARS-CoV-2 infection, TYK2 gene SNPs, i.e. rs2304255, rs2304256, rs12720270, and rs12720354 and ACE2 rs382746 variants, were genotyped in the samples. To confirm the results, the expression of different TYK2 genotypes was investigated using real-time PCR. The presence of the nucleotide T at the locus rs2304255 was shown to be a risk factor linked to disease severity (OR [95% CI] = 3.2485 [2.1554-4.8961]). Similarly, the presence of A at the locus rs12720354 increased the risk of severity (OR [95% CI]) = 3.9721 [2.6075-6.0509]). In contrast, the presence of A at the loci rs2304256 and rs12720270 was observed to reduce the severity risk (OR [95% CI] = 0.2495 [0.1642-0.3793] and 0.1668 [0.1083-0.2569], respectively). Real-time PCR results also demonstrated that the expression level of TYK2 in samples with the TT genotype of rs2304255 and the AA genotype of rs12720354 and in samples with the GG genotype of rs12720207 was significantly lower than in those with other genotypes. The results of this study suggest that TYK2 SNPs might be utilized to identify individuals who are at risk for severe COVID-19, in order to better manage their health care. It is predicted that the presence of some alleles (T in rs2304255, A in rs12720354, and G in rs12720207) of TYK2 can affect COVID-19 severity by reducing TYK2 expression and thereby affecting the regulatory role of TYK2 in the immune response.

Detecting Melanocortin 1 Receptor Gene's SNPs by CRISPR/enAsCas12a.

Beyond its powerful genome-editing capabilities, the CRISPR/Cas system has opened up a new era of molecular diagnostics due to its highly specific base recognition and trans-cleavage activity. However, most CRISPR/Cas detection systems are mainly used to detect nucleic acids of bacteria or viruses, while the application of single nucleotide polymorphism (SNP) detection is limited. The MC1R SNPs were investigated by CRISPR/enAsCas12a and are not limited to the protospacer adjacent motif (PAM) sequence in vitro. Specifically, we optimized the reaction conditions, which proved that the enAsCas12a has a preference for divalent magnesium ion (Mg2+) and can effectively distinguish the genes with a single base difference in the presence of Mg2+, and the Melanocortin l receptor (MC1R) gene with three kinds of SNP sites (T305C, T363C, and G727A) was quantitatively detected. Since the enAsCas12a is not limited by PAM sequence in vitro, the method shown here can extend this extraordinary CRISPR/enAsCas12a detection system to other SNP targets, thus providing a general SNP detection toolbox.

Influence of IL-6 rs1800795 and IL-8 rs2227306 polymorphisms on COVID-19 outcome.

INTRODUCTION: Severe coronavirus disease 2019 (COVID-19) is mainly precipitated by an uncontrolled inflammatory response and cytokine storm. Pro-inflammatory cytokines such as IL-6 and IL-8 levels were markedly increased in complicated cases. Genetic polymorphisms may have a role in this dysregulated expression during SARS-CoV-2 infection. Our aim was to assess the influence of IL-6 and IL-8 single nucleotide polymorphisms (SNPs) on COVID-19 outcomes. METHODOLOGY: 240 subjects were involved in the study; 80 cases with severe COVID-19, 80 cases with mild COVID-19, and 80 healthy subjects. IL-6rs1800795(G/C) and IL-8 rs2227306(C/T) genotyping was performed using real-time polymerase chain reaction (PCR). RESULTS: Ages ranged between 20-67 years in all groups. There was a statistically significant association between the male gender and severe COVID-19. A significantly higher expression of IL-6rs1800795GG and IL-8rs2227306CC genotypes was observed among patients with severe COVID-19 than other groups. At the allele level, IL-6rs1800795G and IL-8rs2227306C alleles were more frequent among patients with severe COVID-19 when compared with other groups. Haplotypes' frequency clarified that the coexistence of IL-6 rs1800795G and IL-8rs2227306C alleles in the same person increased the risk of severe COVID-19 outcomes. Carriers of IL-6rs1800795C and IL-8 rs2227306T alleles are at lower risk of developing severe COVID-19. Multivariate logistic regression analysis showed that old age, male gender, IL-6 rs1800795CG+GG, and IL-8 rs2227306CT+CC genotypes could be independent risk factors for severe COVID-19 outcomes. CONCLUSIONS: IL-6 rs1800795G and IL-8 rs2227306C alleles are significantly associated with severe COVID-19 outcomes, especially if they coexist. They may be used as prognostic markers for COVID-19.

Targeted screening of genetic associations with COVID-19 susceptibility and severity.

The COVID-19 pandemic has resulted in great morbidity and mortality worldwide and human genetic factors have been implicated in the susceptibility and severity of COVID-19. However, few replicate researches have been performed, and studies on associated genes mainly focused on genic regions while regulatory regions were a lack of in-depth dissection. Here, based on previously reported associated variants and genes, we designed a capture panel covering 1,238 candidate variants and 25 regulatory regions of 19 candidate genes and targeted-sequenced 96 mild and 145 severe COVID-19 patients. Genetic association analysis was conducted between mild and severe COVID-19 patients, between all COVID-19 patients and general population, or between severe COVID-19 patients and general population. A total of 49 variants were confirmed to be associated with susceptibility or severity of COVID-19 (p < 0.05), corresponding to 18 independent loci. Specifically, rs1799964 in the promoter of inflammation-related gene TNF, rs9975538 in the intron of interferon receptor gene IFNAR2, rs429358 in the exon of APOE, rs1886814 in the intron of FOXP4-AS1 and a list of variants in the widely reported 3p21.31 and ABO gene were confirmed. It is worth noting that, for the confirmed variants, the phenotypes of the cases and controls were highly consistent between our study and previous reports, and the confirmed variants identified between mild and severe patients were quite different from those identified between patients and general population, suggesting the genetic basis of susceptibility and severity of SARS-CoV-2 infection might be quite different. Moreover, we newly identified 67 significant associated variants in the 12 regulatory regions of 11 candidate genes (p < 0.05). Further annotation by RegulomeDB database and GTEx eQTL data filtered out two variants (rs11246060 and rs28655829) in the enhancer of broad-spectrum antiviral gene IFITM3 that might affect disease severity by regulating the gene expression. Collectively, we confirmed a list of previously reported variants and identified novel regulatory variants associated with susceptibility and severity of COVID-19, which might provide biological and clinical insights into COVID-19 pathogenesis and treatment.

Molecular Study of ACE2 Gene Polymorphism of COVID-19 Infection among the Kurdish Population in Kurdistan Region- Iraq.

Coronavirus Disease 2019 (COVID-19) is a current pandemic infection of the human respiratory system, which is caused by which caused by Sever Acute respiratory syndrome virus 2 (SARS-CoV-2). The infection was classified by World Health Organization (WHO) as a universal pandemic in February 2020; there have been 494.587.638 confirmed cases and 6.170.283 deaths. The present study investigated the molecular genetics of the Angiotensin Converting Enzyme 2 (ACE2) gene in correlation to COVID-19 patients in the Kurdish population. Eighty-six individuals were clinically diagnosed with COVID-19 and control groups. After the genomic DNA extraction these participants the target 1, 2 and 8 exons of the ACE2 gene were amplified using the PCR technique, and then the Sanger sequencing technique was performed to analyze genetic variants of the ACE2 gene in 70 DNA samples of COVID-19 hospital patients at Emergency Hospital in Erbil city, Sarchnar Hospital in Sulaymaniyah city, Lalav Hospital in Duhok city and Wafa Hospital in Halabja city from Kurdistan Region of Iraq. The current study was designed into two groups control group and a patient group. The patient group was divided into two subgroups, severe and mild patients of different ages and genders. As a result, there were no mutations at the positions 1, 2 and 8 exons sequences, while single nucleotide polymorphisms (SNPs) were detected and identified three different types of mutation at intron position: twenty-six of c.12405 del T, two of c.12407 T>G, and two of c.12406 G>A in a total 86 participants. This result shows that genetic difference does not impact the COVID-19 infection severity among the Kurdish population regarding ACE2 gene polymorphism.

Missense Variants of von Willebrand Factor in the Background of COVID-19 Associated Coagulopathy.

COVID-19 associated coagulopathy (CAC), characterized by endothelial dysfunction and hypercoagulability, evokes pulmonary immunothrombosis in advanced COVID-19 cases. Elevated von Willebrand factor (vWF) levels and reduced activities of the ADAMTS13 protease are common in CAC. Here, we aimed to determine whether common genetic variants of these proteins might be associated with COVID-19 severity and hemostatic parameters. A set of single nucleotide polymorphisms (SNPs) in the vWF (rs216311, rs216321, rs1063856, rs1800378, rs1800383) and ADAMTS13 genes (rs2301612, rs28729234, rs34024143) were genotyped in 72 COVID-19 patients. Cross-sectional cohort analysis revealed no association of any polymorphism with disease severity. On the other hand, analysis of variance (ANOVA) uncovered associations with the following clinical parameters: (1) the rs216311 T allele with enhanced INR (international normalized ratio); (2) the rs1800383 C allele with elevated fibrinogen levels; and (3) the rs1063856 C allele with increased red blood cell count, hemoglobin, and creatinine levels. No association could be observed between the phenotypic data and the polymorphisms in the ADAMTS13 gene. Importantly, in silico protein conformational analysis predicted that these missense variants would display global conformational alterations, which might affect the stability and plasma levels of vWF. Our results imply that missense vWF variants might modulate the thrombotic risk in COVID-19.