The Egyptian journal of medical human genetics最新文献

Background: Tumor necrosis factor-alpha (TNFɑ) is a cytokine that manages the host defense mechanism, which may play a role in the pathogenesis of COVID-19 patients. Several single-nucleotide polymorphisms, described in the promoter region of the TNFα gene, have a significant role on its transcriptional activity. These include the - 308A > G polymorphism which increases the TNFα levels with the expression of the A allele. The aim of this study was to explore whether the TNFα.- 308A > G polymorphism affects the clinical state of COVID-19 patients. The study included a total of 1028 individuals infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which were distributed in 3 groups: asymptomatic, mild symptomatic and severe symptomatic patients. The amplification-refractory mutation system was used to determine the genotype of the TNFα.- 308A > G polymorphism.

Results: Results show a higher tendency of being asymptomatic in individuals carrying the GG genotype (336 of 411; OR 1.24, 95% CI 0.91-1.70). The development of a severe form of SARS-CoV-2 infection was not found in subjects with the A allele compared to those with the G allele (OR 0.96, 95% CI 0.51-1.79), except in the eastern region of the country where the risk increased (OR 4.41, 95% CI 1.14-17.05). However, the subjects carrying the A allele had a higher chance of developing symptoms (OR 1.24, 95% CI 0.91-1.70) compared to those with the G allele.

Conclusion: The TNFα.- 308A allele has an influence on developing symptoms of COVID-19 in Cuban patients, and that it particularly increases the risk of presenting severe forms of the disease in the eastern region of the country.

The SARS-CoV-2 has infected many people globally with the ravaging COVID-19; a disease, which has become challenging for every aspect of modern healthcare. The saliva and oral mucosa are sites of high risk for increased viral loads, and aside from the usual epithelial functions like lining and protection, the oral mucosa is also specialized for crucial functions, such as secretion, mastication, sensory perception, and taste perception. The human ACE2 receptor has been extensively studied for its essential role in the regulation of blood pressure homeostasis. However, scRNA-Seq studies have revealed high expression levels of the protein in keratinized epithelial surfaces of the oral cavity. The SARS-CoV-2 have access to the host's body by binding to the ACE2 receptor, leading to the cleavage and major conformational changes in the viral spike glycoprotein for the release of its nucleocapsid into the cellular cytoplasm. This proteolytic cleavage is carried out by the TMPRSS2 and cathepsin L. In this study, we harnessed the information from the binding interface of TMPRSS2 and PAI-1 (a protease inhibitor known to inhibit the TMPRSS2 and several other proteases) to design a potential therapeutic peptide for the inhibition of the TMPRSS2, while also emphasizing the need for preventive masking.

Supplementary information: The online version contains supplementary material available at 10.1186/s43042-022-00213-z.

Background: The angiotensin-converting enzyme-2 (ACE2) is recognized to be the fundamental receptor of severe acute respiratory syndrome coronavirus-2 (SARS-CoV2), responsible for the worldwide Coronavirus Disease-2019 (COVID-19) epidemic. However, genetic differences between people besides racial considerations and their relation to disease susceptibility are still not fully elucidated.

Main body: To uncover the role of ACE2 in COVID-19 infection, we reviewed the published studies that explore the association of COVID-19 with the functional characteristics of ACE2 and its genetic variations. Notably, emerging studies tried to determine whether the ACE2 variants and/or expression could be associated with SARS-CoV/SARS-CoV2 have conflicting results. Some researchers investigated the potential of "population-specific" ACE2 genetic variations to impact the SARS-CoV2 vulnerability and suggested no ethnicity enrichment for ACE2 polymorphisms that could influence SARS-CoV2 S-protein binding. At the same time, some studies use data mining to predict several ACE2 variants that could enhance or decline susceptibility to SARS-CoV. On the other hand, fewer studies revealed an association of ACE2 expression with COVID-19 outcome reporting higher expression levels of ACE2 in East Asians.

Conclusions: ACE2 gene variants and expression may modify the deleterious consequences of SARS-CoV2 to the host cells. It is worth noting that apart from the differences in gene expression and the genetic variations of ACE2, many other environmental and/or genetic factors could modify the disease outcome, including the genes for the innate and the adaptive immune response.

Background: Worldwide, COVID-19's death rate is about 2%, considering the incidence and mortality. However, the information on its complications in other organs, specifically the liver and its disorders, is limited in mild or severe cases. In this study, we aimed to computationally investigate the typical relationships between liver-related diseases [i.e., hepatocellular carcinoma (HCC), and chronic hepatitis B (CHB)] and COVID-19, considering the involved significant genes and their molecular mechanisms.

Methods: We investigated two GEO microarray datasets (GSE164805 and GSE58208) to identify differentially expressed genes (DEGs) among the generated four datasets for mild/severe COVID-19, HCC, and CHB. Then, the overlapping genes among them were identified for GO and KEGG enrichment analyses, protein-protein interaction network construction, hub genes determination, and their associations with immune cell infiltration.

Results: A total of 22 significant genes (i.e., ACTB, ATM, CDC42, DHX15, EPRS, GAPDH, HIF1A, HNRNPA1, HRAS, HSP90AB1, HSPA8, IL1B, JUN, POLR2B, PTPRC, RPS27A, SFRS1, SMARCA4, SRC, TNF, UBE2I, and VEGFA) were found to play essential roles among mild/severe COVID-19 associated with HCC and CHB. Moreover, the analysis of immune cell infiltration revealed that these genes are mostly positively correlated with tumor immune and inflammatory responses.

Conclusions: In summary, the current study demonstrated that 22 identified DEGs might play an essential role in understanding the associations between the mild/severe COVID-19 patients with HCC and CHB. So, the HCC and CHB patients involved in different types of COVID-19 can benefit from immune-based targets for therapeutic interventions.

Supplementary information: The online version contains supplementary material available at 10.1186/s43042-022-00360-3.

Background: Diagnosis of tuberculosis (TB) in the era of technological sophistication requires accuracy and speed to provide as much information as possible so that TB treatment can be carried out quickly and precisely. New studies have also begun to be carried out to diagnose TB, one of which is by examining genes, either by looking at polymorphisms, mutations, or expressions. Several previous studies have confirmed the association of MC3R and TB genes with polymorphisms; MC3R is a gene that participates in the regulation of the inflammatory process and is also found in macrophages; therefore, we tried to analyze gene expression in the active TB group, household contacts, and healthy controls for looked at the differences between the three groups and confirmed the correlation of MC3R with TB by seeing which group's gene expression increased the most expression of the three groups so that the results can be considered as a TB diagnostic biomarker in the future.

Methods: This study included 122 people, 49 patients with confirmed TB, 46 close relatives of patients, and 27 healthy controls. This study used a real-time PCR technique to analyze MC3R gene expression in the three groups, and all data were analyzed using Bio-Rad CFXTM software version 3.1 and one-way ANOVA using SPSS 21.0.

Results: The value of MC3R gene expression in the active TB group increased 3.6-fold in the healthy group (p = 0.143), and that of gene expression in the healthy control group increased 1.09-fold in the healthy group (p = 0.007).

Conclusion: There is a relationship between MC3R and TB based on the results of gene expression analysis that increased in the active TB group compared to the household contact group and healthy controls.

Background: After the first case of COVID-19 being announced in China in December 2019, various diagnostic technologies have been developed at unprecedented pace with the aim of providing a basis for accurate clinical intervention. However, some assays including CRISPR-based diagnostics and loop-mediated isothermal amplification (LAMP) have been less explored. As new COVID-19 technologies emerge, there is need for them to be assessed, validated and improved upon. Moreover, there is paucity of data on the essential factors governing the selection of an appropriate diagnostic approach within the correct timeframe. Myths and origin of SARS-CoV-2 remain to be controversial. Consequently, this review aims at exploring the current COVID-19 diagnostic technologies, performance evaluation, principles, suitability, specificity, sensitivity, successes and challenges of the technologies for laboratory and bedside testing.

Main body: To date, there exist more publications on COVID-19 diagnostics as compared to the Zika virus. The SARS-CoV-2 virus genome profiles were readily available by 31st of December 2019. This was attributed to the fast-paced sharing of the epidemiological and diagnostics data of COVID-19. Timely profiling of the virus genome accelerated the development of diagnostic technologies. Furthermore, the rapid publication of studies that evaluated several diagnostic methods available provided baseline information on how the various technologies work and paved way for development of novel technologies.

Conclusion: Up to date, RT-PCR is the most preferred as compared to the other assays. This is despite the repeated false negatives reported in many of the study findings. Considering that COVID-19 has caused devastating effects on the economy, healthcare systems, agriculture and culture, timely and accurate detection of the virus is paramount in the provision of targeted therapy hence reducing chances of drug resistance, increased treatment costs and morbidity. However, information on the origin of SARS-CoV-2 still remains elusive. Furthermore, knowledge and perception of the patients toward management of SARS-CoV-2 are also paramount to proper diagnosis and management of the pandemic. Future implications of the misperceptions are that they may lead to increased non-compliance to SARS-CoV-2-related World Health Organization (WHO) policies and guidelines.

Background: Given the severe infection, poor prognosis, and the low number of available effective drugs, potential prevention and treatment strategies for COVID-19 need to be urgently developed.

Main body: Herein, we present and discuss the possible protective and therapeutic mechanisms of human microbiota and probiotics based on the previous and recent findings. Microbiota and probiotics consist of mixed cultures of living microorganisms that can positively affect human health through their antiviral, antibacterial, anti-inflammatory, and immunomodulatory effect. In the current study, we address the promising advantages of microbiota and probiotics in decreasing the risk of COVID-19.

Conclusions: Thus, we recommend further studies be conducted for assessing and evaluating the capability of these microbes in the battle against COVID-19.

Background: Coronavirus disease 2019 (COVID-19) is an ongoing pandemic which has emerged as a new challenge for the medical sciences. Severity of COVID-19 is mostly determined with overexpressed proinflammatory cytokines eventually leading to endothelial dysfunction causing vital organ injury, especially in the lungs. It has been postulated that various genetic mutations might be associated with an increased risk of disease severity in COVID-19. This study was thus carried out to determine the association of rs1800896 and rs1800872 genetic polymorphism in IL-10 gene in determining COVID-19 severity.

Methods: The study included 160 RT-PCR confirmed COVID-19 patients with mild (n = 85) and severe (n = 75) conditions. All subjects were genotyped for Interleukin-10 (rs1800896 and rs1800872) gene polymorphisms using PCR-RFLP technique followed by statistical analysis.

Results: This study found a significant gender and age-based discrepancy in COVID-19 severity with 1.85-and 3.81-fold increased risk of COVID-19 in males of mild and severe groups as compared to females (p = 0.046 and p < 0.001) and 4.35-fold high risk in subjects ≥ 50 (p < 0.001). Genotyping analysis showed that IL-10 (rs1800872) gene polymorphism was strongly associated with COVID-19 severity (p = 0.01) whereas, IL-10 rs1800896 polymorphism was not found to confer the risk of COVID-19 severity in our population.

Conclusion: In this regard, the present study provided an evidence that IL-10 (rs1800872) gene polymorphism is strongly associated with COVID-19 severity and CC genotype confer a protective role in preventing severe disease progression. More detailed studies with a larger sample size on the genetic variations are required to establish the role of studied IL-10 gene polymorphisms with COVID-19 severity.

Background: Down syndrome (DS) is characterized by variable degrees of intellectual disability (ID). The coronavirus disease-2019 (COVID-19) lockdown prevented children with DS from reaching their rehabilitation facilities. This could have led to deterioration of their abilities and mental health hazards. The aim of this cohort study was to investigate frequency of COVID-19, the influence of COVID-19 pandemic on health, and some abilities of children with DS, and to explore factors that could have governed receiving home-based training during the lockdown. A survey of 150 individuals with Down syndrome was answered by their caregivers. Additionally, 135 participants were subjected to assessment of cognitive, language, and motor abilities using Portage program. They were divided into 2 groups: group I who received online therapy sessions during the lockdown and group II who did not receive sessions. Logistic regression was used to determine the factors which influenced getting home-based training.

Results: The percentage of COVID-19 cases was 3.3%. All evaluated abilities were reduced despite receiving online sessions particularly language performance (P < 0.001). Male gender, having severe ID and low parental education were among the factors which encouraged parents to get virtual training.

Conclusion: COVID-19 pandemic had a negative impact on the abilities of DS children even those who got rehabilitation sessions. Their dependence on social interaction could have limited the benefit of virtual sessions. Factors that influence a parent's decision to get home-based training should be monitored and targeted in order to overcome obstacles or concepts that may prevent families from enduring home-based intervention.