Human Gene最新文献

Angiotensin-converting enzyme 2 (ACE2) and the transmembrane serine protease 2 (TMPRSS2) are recognized as entry proteins of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and recently their Single Nucleotide Polymorphisms (SNP) have been studied in different populations to elucidate the impact on disease. This study aimed to evaluate the genetic SNP of ACE2 (rs35803318) and TMPRSS2 (rs2070788) genes in COVID-19 patients from Northeast Brazil compared with global populations, as well as the expression quantitative trait locus (eQTL). For ACE2 (rs35803318), we found 92.6% CC, 3.4% CT, and 4.0% TT genotype carriers in SARS-CoV-2-positive patients. Surprisingly, only the genotype frequencies of ACE2 SNP were not in Hardy-Weinberg equilibrium. For TMPRSS2 rs2070788, we found 22.3% GG, 50.7% AG, and 27% AA genotype carriers in SARS-CoV-2-positive patients. The expression quantitative trait loci (eQTLs) revealed that rs35803318 was associated with an altered PIR gene expression, and rs2070788 was found to eQTLs association only with lung tissue. No significant association was identified between the genotype distribution of SNPs and the ‘patient's outcome. In conclusion, our results suggest that ACE2 and TMPRSS2 may not be protective factors for global populations, including the Brazilian population, since the presence of SNPs does not affect the ‘patient's outcome as described by other studies.

Acute lymphoblastic leukemia (ALL), manifested by the rapid proliferation of blasts in the bone marrow, is the most prevalent pediatric malignancy; however, it could also be detected in the adults. Autophagy is a programmed catabolic process involved in the maintenance of cell homeostasis through destruction of damaged organs and misfolded proteins. Disruption of autophagy leads to abnormalities in cellular processes associated with cancer and acts as a double-edged sword. Although in a number of cancers, the suppression of autophagy resulted in a tumorigenesis process, in other types of this disease, the activation of this process may participate in the maintenance of cell survival. In this study, we evaluated the expression of Beclin1, Atg7 and Atg10 genes in 50 patients diagnosed with de novo B-ALL in comparison with 18 healthy counterparts using relative-quantitative real time-PCR. The majority of B-ALL patients showed a significant reduction in the expression of aforementioned genes as compared to the control group (P < 0.05). Moreover, we found a positive correlation between Beclin1 and Atg7 expression level in the patients (P < 0.001 and r = 0.57). These findings suggested that probably any disruption in the regulation of autophagy could be involved in leukemogenesis and thereby autophagy could be regarded as a valuable therapeutic target to eliminate the leukemic cells.

MicroRNA (miRNA) is a small and non-coding RNA that can control the post-transcriptional expressions of many downstream targets. Several in vitro, in vivo, and clinical studies have reported the putative tumour-modulatory roles of miR-4319 in multiple human cancers. However, an effective review article that could summarize the findings of the tumour-regulatory functions of miR-4319 in human cancers is scarce. To bridge the gap in the literature, this review aimed to unravel the tumour-regulatory roles of miR-4319 by integrating the findings from various original research articles. Overall, miR-4319 is underexpressed in at least 14 human cancers, suggesting its downregulation is linked to cancer progression. Further analyses of the data from various literatures showed that besides influencing the translational repression of different downstream targets, miR-4319 could also interact with seven types of long non-coding RNA (lncRNA) (LINC00667, HOXA-AS3, CPLC, GNAS-AS1, DANCR, PCAT18, and TNK2-AS1) and two types of circular RNA (circRNA) (circATXN7 and circ_0058058). Dysregulation of these interactions can facilitate cancer development. Considering the observations that miR-4319 is downregulated in many cancer types, it has a promising role to be employed as a diagnostic biomarker. Besides, the upregulation of miR-4319 is also associated with good clinical outcomes in colorectal, liver, and prostate cancers, making miR-4319 a potential candidate as a prognostic biomarker. Additionally, overexpressing miR-4319 could potentially help slow cancer progression. Although miR-4319 has the potential to be utilized as a biomarker or therapeutic agent, more future studies, including clinical trials with a scale-able sample size, should be conducted to validate the accuracy, reliability, safety, sensitivity, and specificity of miR-4319 as a biomarker or therapeutic agent.

Aim

The anti-inflammatory and pro-inflammatory cytokine genes are linked to the severity and prognosis of individuals with respiratory and non-respiratory viral infections. The present investigation aimed to evaluate the association between the cytokine (IL10 rs1800872 & TNF rs1800629) gene polymorphisms and the severity of COVID-19 severity.

Methods

The PubMed, Elsevier, Science Direct, and EMBASE databases were utilized for a comprehensive literature review to find suitable case-control studies that investigate the relationship between the IL10 rs1800872 and TNF rs1800629 gene polymorphisms and COVID-19 severity. The articles included in the investigation provided the genotypic data for analysis and meet the inclusion criteria. Each model was assessed with a 95% confidence interval (CI) and odds ratio (OR), with significance set at p < 0.05 for IL10 rs1800872 and TNF rs1800629 gene polymorphisms. MetaGenyo software was used to conduct a meta-analysis for assessing the statistical significance. The study quality was assessed using the Rob2 tool.

Results

Totally 3994 COVID-19 cases and 3504 controls in eleven studies were examined to identify the relationship between IL10 rs1800872 & TNF rs1800629 gene polymorphisms and the severity of COVID-19 in Asian and Caucasian populations. The findings revealed that there was a notable association between the TNF rs1800629 gene polymorphism and the COVID-19 severity, with a p-value <0.05 indicating statistical significance. However, no association was found between the IL10 rs1800872 gene polymorphism and the severity of COVID-19 with a p-value >0.05 suggesting insignificance. Furthermore, the findings were confirmed with the funnel plot analysis, which demonstrated the statistical validity of the results.

Conclusion

The TNF rs1800629 gene polymorphism is a risk factor for the severity of COVID-19 and the IL10 rs1800872 gene polymorphism does not have any association with the severity of COVID-19. Therefore, the TNF gene plays a role in the development of severe COVID-19 and it can be used as a biomarker for diagnosis of COVID-19.

Background

Alzheimer's disease, the most common form of dementia, accounts for 60–80% of cases and its prevalence is projected to increase as aging populations grow. By 2050, the number of individuals with Alzheimer's and dementia worldwide is expected to reach 152 million. Genetics plays a significant role, contributing to about 70% of the overall risk, underscoring the importance of understanding the genetic basis for developing targeted interventions. This study presents a system that combines text mining and machine learning techniques to identify and prioritize prospective candidate genes for Alzheimer's and further classifies them into three association classes with weights.

Methods

The machine learning-based classifier was trained over a meticulously curated gold standard dataset and then rigorously validated utilizing a 10-fold cross-validation method, demonstrating its consistency across all the folds of the data. This developed ensemble learning system categorizes PubMed abstracts into three distinct groups: Yes, No, and Ambiguous using text mining and a Bayesian classification algorithm. The system further predicts disease-gene associations over unknown disease-specific prediction data by using the developed classifier.

Results

With an average accuracy of 87.33% and confidence level of 90.10% +/− 0.142, the protocol effectively extracted 2031 associated genes, of which 1162, 489 and 1439 belong to positive, negative and ambiguous classes respectively at the threshold of 0.9. In comparison between the established disease gene databases, our system identified 915 positive genes that had not been previously reported. One can use these positive genes for in-depth understanding and ambiguous genes for further exploration of their association with Alzheimer's disease.

Conclusions

The system's ability to generate accurate predictions demonstrates its robustness and provides valuable insights into the genetic factors of Alzheimer's disease. Consequently, this study contributes to existing knowledge and paves the way for future research in this field.

The calpain-10 gene (CAPN10) was the first gene identified to be associated with Type 2 diabetes mellitus. Several polymorphic loci of the calpain-10 gene (CAPN10) have been implicated in the etiology of Type 2 diabetes mellitus. However, the results have been conflicting. Keeping this in view, the present study was aimed at doing a meta-analysis to dig out the association of CAPN SNP 44 (rs2975760) polymorphism with type 2 diabetes mellitus, given that the role of polymorphism at this particular locus is lesser studied than the rest and therefore shrouded in speculations.

Preferred Reporting Items for Systematic Reviews and Meta-analyses PRISMA and the published PROSPERO research protocol was followed for the present study. A total of thirteen studies were included for pooling of data. All statistical analyses were done on R studio (version 4.2.3). The meta-analysis has lead to the conclusion that the genotype ‘CC' has significantly low odds of occurrence in the type 2 diabetes mellitus patients in the Middle Eastern Populations. Therefore, we postulate that the minor allele ‘C' must be playing a protective role against type 2 diabetes mellitus. However, the question of how the ‘CC' genotype must be affecting the incidence of T2DM only the Middle Eastern populations remains to be answered.

Pancreatic cancers include highly aggressive forms of neoplasms, with limited treatment options and high mortality rates. Recent studies have highlighted various molecular pathways underlying the dynamic modification of the coagulation cascade by pancreatic cancer cells, promoting the development of thromboembolic events and possibly contributing to tumor progression. As such, the use of anticoagulants as adjuncts to chemotherapy in the treatment of pancreatic neoplasms has become a topic of interest. A literature review of over 115 articles was conducted. The primary objective was to highlight the molecular pathways implicated in both pancreatic cancer and the coagulation cascade, as well as the influence of anti-coagulants on cancer related thromboembolic events and their potential use as anti-metastatic medications. Available data suggests significant reduction in thromboembolic events following adjunct treatment with anticoagulants, though an impact on overall survival remains poorly characterized. Several anti-coagulants were found to have prominent anti-metastatic effects, and in animal models improved overall survival and decreased tumor growth margins. Gene pathways such as Protease-Activated Receptor-1 (PAR-1) and Kirsten rat sarcoma viral oncogene (KRAS) are also heavily upregulated in the context of pancreatic cancer and further modified by anti-coagulant use. Further studies are needed to characterize the risks and efficacy of this treatment option in humans.

Background

Abnormal expression of microRNAs is one of the crucial features contributing to the thyroid cancer (TC) progression. However, a comprehensive identification of the dysregulated microRNA profile and the associated molecular pathways that underlie the TC pathogenesis has not been completely provided. In the current study, bioinformatic analysis tools and microarray datasets were used to evaluate the biological roles of differentially expressed microRNAs and their targets in TC.

Methods

GEO2R was used to identify differentially expressed microRNAs in TC samples. The mRNA targets of these microRNAs were predicted using different databases. DAVID and Reactome databases were used to perform gene ontology and pathway enrichment analyses of target genes. Then, the protein-protein interaction networks were constructed among them through the STRING database. MCODE was applied to screen hub genes. The prognostic values of hub genes were examined in TCGA THCA dataset using GEPIA2 platform. The relationship between hub genes and the ERBB2 protein was revealed using GeneMANIA.

Results

We found a significant decrease in five microRNAs and a significant increase in five others in TC samples. Target genes of upregulated and downregulated microRNAs in TC were associated with ERBB2 signaling and ion exchanger pathways, respectively. CUX2 and DCUN1D4, the targets of upregulated microRNAs, were downregulated, whereas AP1S1, the target of downregulated microRNAs, were overexpressed in TCGA THCA samples. EZR and CUL5 were mediators for the interaction of ERBB2 with CUX2 or DCUN1D4, respectively.

Conclusion

We suggest that CUX2/DCUN1D4 and AP1S1 may act as tumor suppressor and oncogene in TC onset and progression, respectively.

The severity of Coronavirus Disease 2019 (COVID-19) has been closely linked to an exacerbated proinflammatory response and cytokine storm. Interleukin-1 (IL-1), a pivotal proinflammatory cytokine, plays a crucial role in the development of acute respiratory distress syndrome (ARDS) and multiorgan dysfunction. Single nucleotide polymorphisms within the IL-1 gene have been shown to modulate IL-1 cytokine levels. This study aimed to investigate the association of IL-1 gene polymorphisms (IL-1 + 3953C > T, IL-1β -511 T > C, and IL-1Ra) with the severity of COVID-19. Genotyping of IL-1 gene polymorphisms (IL-1 + 3953C > T, IL-1β -511 T > C) were performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), while IL-1Ra genotyping was done by Random Amplification of Polymorphic DNA (RAPD). PCR-RFLP data were validated through Sanger sequencing (SeqStudio Genetic Analyzer). Data analysis was carried out by SPSS-v21 and SHesis (online version). The frequency of the T allele of the IL-1 + 3953C > T polymorphism was found to be higher in mild cases as compared to severe cases, demonstrating a significant protective effect against COVID-19 severity (P = 0.001). However, no significant associations were observed for IL-1β -511 T > C and IL-1Ra polymorphisms (P > 0.05). In haplotype analysis (between IL-1 + 3953C > T, and IL-1β -511 T > C gene polymorphisms), individual with CT haplotype showed a higher risk of severity (OR = 1.8, P = 0.001), while individuals with TT haplotype showed significant protection against severity (P = 0.001). Our findings suggest that the T allele of IL-1β + 3953C > T polymorphism may confer protective effect against the severity of COVID-19.

Background

The components of oral microorganisms are important for stimulating the production of pro-inflammatory cytokines, making it essential to understand this relationship. The purpose of this research was to investigate the relationship between polymorphisms of Interleukin 10 (IL-10) and Interleukin 6(IL-6) and candidiasis-type tooth decay.

Methods

Two hundred and forty individuals, including120 patients and 120 controls provided saliva and blood samples in accordance with ethical standards. Saliva samples were cultured on SDA and PDA to detect fungi, which were then identified using confirmatory tests. Additionally, blood samples were assayed to detect IL6 rs1800795, IL10 rs1800871 and rs1800872 genotypes. The relationship between these polymorphisms and candidiasis-type tooth decay was then investigated using the SPSS statistical program.

Results

Six types of dental caries were identified: Candida albicans (C.albicans) (75.25%), C. parapsilosis(20.58%), C. glabrata (4.54%), C. krusei (9.8%), Rhodotorula spp. (4.54%) and Penicillium spp. (5.44%). The allelic distribution of IL6 (−147 G/C) SNP (rs1800795) showed no statistically significant difference(P values for G/C and CC genotypes, respectively, p = 0.57 and p = 0.42). In addition, the presence The C allele increases the probability of contracting the disease by 1.3 times compared to the healthy group. But these effects are not statistically significant (P = 0.67). The rs1800871 T/C, it has no effect on the occurrence of the disease (OR = 0.37, 95% CI = 0.8–1.2). However, the C/C genotype increases the probability of tooth decay by 6 times (OR = 6, 95%, CI = 1.8–19.0, p = 0.01) and the C allele increases the likelihood of developing dental caries by 3.5 times (OR = 3.5, 95%, CI = 1.6–7.4) compared to the healthy group (p = 0.017).Also, the rs1800872 polymorphism, the A/C genotype does not have an effect on the incidence of the disease (OR = 0.44, 95% CI =0.1–1.97, p > 0.2) while the C/C genotype is more likely to suffer from caries. Caries increases 2.7 times compared to the AA genotype (OR = 2.7, 95% CI = 0.8–8.5, p = 0.09), and the C allele compared to the A allele increases the probability of periodontitis up to 2.4 times (OR = 2.4, 95% CI = 0.9–5.9, p = 0.05).

Conclusion

There may be a correlation between IL6 rs1800795, IL10 rs1800871 and 1,800,872 polymorphisms with periodontitis. However, further investigation with a larger sample size is needed to explore this relationship.