Numerous risk factors related to the coronavirus were identified, encompassing demographics such as age, sex, diabetes, hypertension, obesity, and geographical region (Buscemi et al., 2021). Furthermore, it is important to acknowledge that genetic characteristics suffer from an important impact in becoming susceptible toward SARS-CoV-2 infected. The sensitivity individuals to SARS-CoV-2 infected is linked to a great deal of genetic polymorphisms (variants) in multiple genes, specifically responsible for encoding host receptors that are involved in the entry of the virus process and triggering immune system cells. Mutations in genes possess the ability to be hereditary, passing from one generation of people to the next, and can be noticed in a minimum of 1% of the people within a specific group. This phenomenon may provide an explanation for the variations in vulnerability to certain diseases, like COVID-19 (Kaltoum,2021).

Genetic variation happens within and between populations, resulting in polymorphisms that may be associated with a genetic characteristic or a phenotype in the presence of an environmental stimulus (Hirschhorn and Daly, 2005).

Single-nucleotide polymorphisms (SNPs) are the most prevalent type of polymorphism identified in the human genome, accounting for 90% of all genetic changes between individuals. SNPs are the most prevalent type of genetic variation and are widely utilized to analyze genetic differences between people and communities. These SNPs may have a role in changes to the genomic sequence (van Dijk et al., 2014). These genetic polymorphisms may have an impact on the outcome of COVID-19 in high or intermediate producers of this cytokine (Silva et al., 2022).

The relationship between immune gene polymorphisms and the outcome of viral infections has long been a source of interest. Because of the role of these genes in viral clearance and immunopathogenesis, variations in these regions are expected to influence the outcome of a disease like COVID-19 (Hashemi et al., 2021).

The susceptibility or resistance to several viral infections is known to be significantly influenced by host genetic polymorphisms, Because of the role of host genes in the entry and replication of SARS-CoV-2 in cells, as well as the development of an immune response, it appears that a combination of many genes may be involved in COVID-19 pathogenesis (Debnath et al., 2020). As a result, various research on the relationship between genetic polymorphisms and COVID-19 have been performed to date (Elhabyan et al., 2020).

Major changes in cytokine genes have the potential for influencing the generation of cytokines, whereas even slight alterations in such genes may accumulate over time in humanity that result in a substantial plausible biological effect (Cooper, 2003, Bidwell et al., 1999). Ahir et al., (2015) have identified numerous its (SNPs) throughout the genes that encode cytokines as well as the receptors for them which demonstrate a strong correlation between the emergence in addition outcome of multiple illnesses.

Variations in COVID19 prevalence and mortality rates among countries may be explained by polymorphisms in various interleukins genes (Karcioglu Batur and Hekim,2021).

Among cells of interest that expressed chemokine receptors are monocytes, dendritic of cells in addition to lymphocytes and basophils. Notably to this, it should be noted which the CCR2 receptor can be detected on non-hematopoietic cell types like endothelially, fibroblasts and mesenchymal stem cells (Salcedo et al., 2000). Monocytes are cells exhibit a constant production of CCR2. During an induction of monocytes, there has been an observed rise in the amount of expression of CCR2, which is analogous to the greater expression detected onto lymphocytes response for activation using IL-2 (Luster,1998), reported a study of the association of CCR2 SNP V64I gene polymorphism in patients with severity COVID-19 infections to reveal more immune routes leading to towards the seriousness as well as mortality of a disease (Dogan et al., 2022).

Interleukin 6 receptor rs4845374 and rs2228145 SNP

The potential influence of a persons genetic variation on disparities in the immune system's reaction among people infected via the novel coronavirus illness is able to be investigated through looking at the potential linkage between polymorphisms within particular genes and rates of infection and death from SARS-CoV-2 in various international populations (Karcioglu Batur and Hekim,2021).

The researcher team in Italian in investigated the distribution of genetic variations IL-6R genes (rs2228144, rs2229237, rs2228145, rs28730735, rs143810642), which may be employed as prognostic and pharmacogenetic biomarkers for COVID-19. These variants have been predicted to affect the expression and binding ability of IL6 and IL-6R . additionally, showed that IL6 and IL-6R appeared to be implicated in several pathogenetic mechanisms associated with COVID19 severity and mortality. Thus, the availability of IL6-IL-6R-related biomarkers for COVID19 disease may be helpful to counteract harmful complications and prevent multi-organ failure. Finally, researchers concluded, how IL6 and IL-6R pleiotropic activity could be exploited to meet different clinical needs and realize precision medicine protocols for cases public health emergencies (Strafella et al., 2020).

The predisposition and disease progression of COVID-19 are influenced via recipient genetic variations, especially that relate to immune system reactions. Some polymorphisms of cytokines and chemokines receptors have been discovered determined for being linked to the development of COVID-19, based on the impact of the happening variability. For instance, polymorphisms made up of single nucleotide within the TNF locus have been related associated greater severity and strong inflammatory reactions. While presence of genetic polymorphisms in four types of Tolls like receptors (3,4,7 and 9) genes may be associated with an increase of serious breathing problems among people suffer from COVID-19 (Vakil et al., 2022). Previous studies also reported that rs2228145 SNPs of interleukin 6 receptors were linked to manifestations severe COVID-19 infections (Smieszek et al., 2021).

A highly prevalent missense mutation within the IL-6R locus has been identified at the rs2228145 loci. Notably, it was projected to have consequences for protein activity because of the arrangement of amino acids. The modification takes place within the extracellular portion of the receptor, that plays a crucial role in the interaction between IL-6R in addition exogenous ligands. Hence, it is plausible that the genetic variation could modify the structural arrangement of the protein domain, thereby potentially impeding the determination of IL-6, which Indeed, there exists some association in between the rs2228145 genetic variant as well as elevated amounts of soluble IL-6R in circulation. According to Garbers et al. (2018) and Cavieres et al. (2019), The IL-6 receptor locus (IL-6R Asp358Ala; rs2228145 A>C) exhibits a prevalent polymorphism which has been connected to elevated the amount of serum sIL-6R. This variant in the gene is thought to be linked with numerous diseases associated with inflammatory disease (Garbers et al., 2014).

The analysis of population variations related to polymorphism of IL-6R located at the rs2228145 locus indicates that the majority of governments demonstrate the AC genotype, with the exception of India and the country of Sweden, where the AA genotype is predominantly seen. As of September 2020, a comparison of COVID-19 infection rates and fatalities by country, revealed that Spain and Brazil exhibited the most considerable values in terms of both COVID-19 infections as well as mortality levels (Karcioglu Batur and Hekim ,2021).

The rs2228145 variant is a missense mutation that has been identified as an important contributor influencing the levels of IL-6R in several bodily fluids (Garbers et al., 2018; Strafella et al., 2020). The previously mentioned mutation in IL-6R is essential for its ability to bind to external ligands. There was a theory that suggested an amino acid return, namely the substitution of aspartic acid for alanine at position 358 (p.Asp358Ala), would have an impact on protein function (Strafella et al., 2020).

CC chemokine receptor 2 (rs1799864 SNP)

Chemokines have played a pivotal role in facilitating a immunological defense against viral infections. The interaction between the chemokines in addition to their corresponding receptors is of crucial significance in beginning and regulating and recruitment as well promotion of the immune system's cells inside the infected alveoli (Domingo-Gonzalez et al.,2016). The CCR2 plays an indispensable part in the recruitment of both immunological as well non-immunological cells during pathological circumstances. It functions as a receptor for monocyte chemoattractant protein-1 (MCP-1) (Kirsten et al., 2005).

The genetic intermediaries CCR2 has been identified to be genetically associated with serious illnesses triggered by Novel coronavirus through an impartial investigation of the molecular strategies underlying this their phenotype. the researcher focused on finding potential causal variants and determined that serious COVID-19 is correlated with CCR2 mutations that are predictive of elevated levels of CCR2 within pulmonary tissue (Zhou et al., 2020b). it is CCR2 receptor responsible for binding to CCL2, often referred to as MCP-1, is also known as CCR2. The attraction of monocytes and macrophages towards locations of COVID-19 infection is facilitated through the CCL2/CCR2 pathway. Excessive activation within this axis triggers excessive inflammation with subsequent damage to organs. (Zhao et al., 2020).

The CCR2 locus is located at chromosomal 3p21, particularly within a collection of genes which generate chemokine receptors. The CCR2 DNA produces dual isoforms, namely CCR2A and CCR2B. The CCR2 gene has a single nucleotide polymorphism (SNP) where a guanine (G) is substituted with an adenine (A) at nucleotide 190. This modification results in a protein's amino acid shift from valine (GTC) for isoleucine (ATC) at position 64, resulting to the designation CCR2-V64I. The aforementioned peptide replacement, that's of a conservative nature, arises inside the primary transmembrane area for both CCR2A and CCR2B. This substitution results in more stability and prolonged half-life specifically for CCR2A, while having no discernible impact on the stability of the CCR2B isoform (Nakayama et al., 2004). This CCR2-V64I polymorphisms is being subject to important investigation, with several studies demonstrating a correlation between the presence of the CCR2-64I variant as well as a decreased likelihood of AIDS development among people infected by HIV, in addition to a lower susceptibility to diseases such as multiple sclerosis and also the development of breast cancer (Fatima-Zahra et al., 2020).

Some study mentioned, participants immunological phenotype/genotype information can assist researchers to genetically comprehend the infection with SARS-CoV-2 as well as detect illness progression. Chemokines are being implicated in the outbreaks of SARS and MERS, which can additionally contribute to COVID 19 symptoms. and researcher observed evaluated relationship between multiple chemoattract types of SNP, especially CCR2-V64I DNA mutations and COVID-19 severity for identify immunological mechanisms causing sickness severity and also mortality (Dogan et al., 2022). CCR2-V64I mutations can impact risk of COVID-19 infections throughout Asian countries (Chen et al., 2011).

According to some articles, COVID-19 patients had greater quantities of multiple chemokines and cytokines compared to controls, regardless of their sex. The upregulation of CCR2 levels appeared to be more pronounced among individuals who experienced a more serious medical condition throughout the time they were hospitalized (Pomar et al., 2022).

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مواضيع ذات صلة

Adenovirus Coinfection with SARS-CoV-2

Acute viral hepatitis

Human receptor of coronavirus and Adenovirus

Antiviral Chemotherapy

Humoral Immune Responses to SARS-CoV-2 Infection

Cellular Immune Responses to SARS-CoV-2

Pathogenesis of SARS-CoV-2

Epidemiology of SARS-CoV-2

PARVOVIRIDAE

تركيب فيروس التهاب الكبد الوبائي نوع ب الخفي

REPLICATION OF VIRUSES AN OVERVIEW

مرض الجدري Smallpox