Meta Gene最新文献

Coronavirus disease 19 (COVID-19) is a highly contagious respiratory viral infection. Dysregulated immune response is an important feature of disease, and cytokines are among the most important mediators of dysregulated immunity. Interleukin-37 (IL-37) is one such cytokine and studies have indicated its role in pathogenesis of COVID-19. However, IL37 gene polymorphisms have not been identified in patients with COVID-19. Therefore, this case-control study (100 patients and 100 controls) was performed to understand the role six single nucleotide polymorphisms of IL37 gene (SNPs: rs3811042, rs3811043, rs2466449, rs3811045, rs3811046 and rs3811047) in susceptibility to COVID-19 among cases with severe disease. These polymorphisms were identified by Sanger DNA sequencing. Results revealed that TG genotype of rs3811046 showed a significantly increased frequency in patients compared to controls (61.0 vs. 38.0%; odds ratio [OR] = 2.55; 95% confidence interval [CI] = 1.45–4.50; probability [p] = 0.002; corrected p [pc] = 0.01). GA genotype of rs3811047 also showed an increased frequency in patients but the pc-value was not significant (39.0 vs. 24.0%; OR = 2.02; 95% CI = 1.10–3.71; p = 0.033; pc = 0.165). Haplotype analysis revealed a significantly increased frequency of the haplotype G-C-A-T-T-A (in the order: rs3811042, rs3811043, rs2466449, rs3811045, rs3811046 and rs3811047) in COVID-19 patients compared to controls (0.055 vs. 0.006; OR = 10.23; 95% CI = 1.53–68.14; p = 0.003; pc = 0.03). In conclusion, the study indicated that two variants of IL37 gene (rs3811046 and rs3811047) may be associated with susceptibility to COVID-19 among Iraqi population.

We revisit the topic of human genome guanine-cytosine (G+C) content and adenine-thymine (A+T) content under neutral evolution. For this study, the “gold standard” de novo mutation data within the human genome is used to estimate the mutation rates, instead of using base substitution data between related species. We define the rates (coefficients) of de novo mutation events, which are estimated solely from the mutation event data. Based on the de novo mutations collected from the intergenic regions of control samples, we are able to calculate the limiting content of any genomic quantities, by calculating the components of the normalized eigenvector corresponding to the largest eigenvalue of the transpose of the mutational rates matrix. When a 3-by-3 mutational rate matrix is used, accounting for the G+C content, A+T content, and CpG density, their neutral limit at time infinity is obtained. We observe that the G+C content in the currently G+C rich regions drops less severely than in the G+C poor regions. This provides a potential mechanism to retain the current spatial variation of G+C content (isochore-like structure), and to resist against homogenization.

Diabetic nephropathy (DN) was considered as the major cause of end-stage renal disease (ESRD) with the high mortality rate in the affected patients. Patients with DN are at high risk of death from cardiovascular diseases. C-reactive protein (CRP) gene has been known to be effective in the pathogenesis of renal and cardiovascular disease. The aim of the present study was to investigate the association between two CRP polymorphisms, rs2794521 and rs1800947, and risk of DN. Seventy-five patients with DN, fifty patients with diabetic mellitus and fifty healthy controls were enrolled. The genotyping of rs2794521 and rs1800947 were done by using PCR-RFLP. The analysis of the results indicated that rs2794521 was significantly associated with susceptibility to DN but no diabetic mellitus. No association was observed between rs1800947 and the DN risk. The obtained data suggested that rs2794521 may play a role in the etiology of DN.

Researchers have consistently linked some TCF7L2 gene variations, such as rs7903146, rs12255372, and rs11255372, to Type 2 diabetes mellitus (T2DM) in numerous populations and ethnic groups. The goal of this study is to show if the TCF7L2 variations rs4506565 T/A is linked to T2DM in Iraqi Arab patients. For this purpose, a case-control study was conducted with 100 T2DM patients and 100 controls. The Tetra-Primer ARMS-PCR Technique was used to genotype TCF7L2 rs4506565 T/A, making use of newly-designed primers. The study concluded that the TCF7L2 gene polymorphism rs4506565 T/A shows no significant difference in genotypes in any of the codominant, dominant, over dominant, recessive, and additive models. The dominant model has a significance with age but no significance with other parameters.

Nephrotic syndrome (NS) remains the most frequent indication of glomerular disease in childhood. The NPHS1 gene encoding nephrin protein is one of the common mutant genes in SRNS (Steroid Resistant Nephrotic syndrome) patients. These gene mutations are more likely to progress into ESKD (end-stage kidney disease). In the present study, we investigated the pathogenesis of the NPHS1 gene in Indian patients with SSNS and SRNS. Ninety-six children have been involved in the present study in which 37 belong to Steroid Sensitive Nephrotic syndrome (SSNS), 27 belong to Steroid Resistant Nephrotic syndrome (SRNS) 32 are healthy individuals. We designed a panel of NPHS1 gene (CDS- Coding sequence) and performed Illumina sequencing (MiSeq). We found a total of 45 variants in the NPHS1 gene. In addition, we found novel pathogenic c.2441A > G and two likely pathogenic missense variants, p.Gly395Ser, p.Ser400Pro in SSNS and SRNS patients by ACMG criteria. Therefore, early diagnosis of steroid resistant nephrotic syndrome in the Indian population can be made by identifying genetic variants using a customized gene panel.

Background

Coronavirus disease 2019 is characterized by the elevation of a broad spectrum of inflammatory mediators associated with poor disease outcomes. We aimed at an in-silico analysis of regulatory microRNA and their transcription factors (TF) for these inflammatory genes that may help to devise potential therapeutic strategies in the future.

Methods

The cytokine regulating immune-expressed genes (CRIEG) were sorted from literature and the GEO microarray dataset. Their co-differentially expressed miRNA and transcription factors were predicted from publicly available databases. Enrichment analysis was done through mienturnet, MiEAA, Gene Ontology, and pathways predicted by KEGG and Reactome pathways. Finally, the functional and regulatory features were analyzed and visualized through Cytoscape.

Results

Sixteen CRIEG were observed to have a significant protein-protein interaction network. The ontological analysis revealed significantly enriched pathways for biological processes, molecular functions, and cellular components. The search performed in the miRNA database yielded ten miRNAs that are significantly involved in regulating these genes and their transcription factors.

Conclusion

An in-silico representation of a network involving miRNAs, CRIEGs, and TF, which take part in the inflammatory response in COVID-19, has been elucidated. Thus, these regulatory factors may have potentially critical roles in the inflammatory response in COVID-19 and may be explored further to develop targeted therapeutic strategies and mechanistic validation.

Breast cancer represents the leading cause of cancer-related death in women globally. Obesity is one of the risk factors for breast cancer, particularly in postmenopausal women. Adiposopathy causes hypertrophy, which promotes metabolic dysregulation, hypoxia, inflammation, insulin resistance, and altered adipokine production such as vaspin and omentin-1. The objective of this study is to inspect the link between the vaspin rs2236242 and the Val109Asp omentin gene polymorphisms and their serum levels with breast cancer occurrence in postmenopausal females. The gene polymorphisms of vaspin rs2236242 and Val109Asp omentin were identified by T-ARMS-PCR and PCR-RFLP respectively. The glucose homeostasis traits, lipid profile, total antioxidant capacity, and circulating vaspin and omentin-1 levels were all assessed. The AT genotype of vaspin rs2236242 and the Val/Asp genotype of Val109Asp omentin were more prominent in breast cancer patients than the TT and Asp/Asp genotypes respectively. Breast cancer patients showed significant lower levels of serum vaspin and omentin-1. The AT genotype of the vaspin rs2236242 polymorphism, the heterozygous Asp/Val genotype of the omentin-1 gene, and low serum vaspin and omentin-1 levels are more associated with breast cancer incidence. On the flip side, higher levels of serum vaspin and omentin appear to protect against the incidence of breast cancer.

Susceptibility to coronavirus disease 2019 (COVID-19) and disease severity has recently been associated with inflammatory markers and genetic polymorphisms of ACE (angiotensin-converting enzyme) and ACE2 genes, but the evidence has been inconclusive. This case-control study (99 COVID-19 patients and 96 controls) sought to assess the significance of age, C-reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR) and SARS-CoV-2 RT-PCR cycle threshold (Ct) in severity of COVID-19. Besides, two variants of ACE and ACE2 genes (rs4646994 and rs2285666, respectively) were analyzed to determine their role in COVID-19 susceptibility and/or disease severity. Results revealed that age, CRP and NLR were significantly elevated in severe cases compared to moderate cases, while RT-PCR Ct value was significantly decreased. Allele and genotypes of both variants were not associated with COVID-19 risk, with the exception of rs2285666 A allele. It showed a significantly higher frequency in female patients than in female controls (probability = 0.041). In conclusion, the study indicated the role of age, CRP, NLR and SARS-CoV-2 RT-PCR Ct in susceptibility to COVID-19 severity. However, analysis of the ACE and ACE2 gene variants (rs4646994 and rs2285666, respectively) showed that the two variants were not associated with the risk of developing COVID-19.

The unleased proliferation of lymphoid progenitor cells could result in Acute lymphoblastic leukemia (ALL). The early diagnosis of this malignancy, with high prevalence in children and poor prognosis in adults, has remained a big challenge. Single Nucleotide Polymorphisms (SNPs) could be studied as potent genetic factors to be used as the diagnosis and prognosis biomarkers. Although some SNPs with significant association with the risk of ALL have been reported, more studies are needed to improve the list of these biomarkers to better predict the risk of ALL cancer. In this study, we selected and genotyped eight SNPs in ALL patients and healthy controls using the tetra-primer ARMS PCR method. The outcomes significantly revealed that the presence of different alleles at the SNPs positions could manipulate the risk of ALL incidence. These SNPs include rs10757278, rs1800472, rs12430881, rs35958982, rs1946518, rs4073, rs3813865 and rs889312. The data obtained from this work might have implications in clinics.

Antisense non-coding RNA at the INK4 locus (ANRIL) is a long non-coding transcript localized within, and antisense to, the genes encoding the cyclin-dependent kinase inhibitor-2A/B (CDKN2A/B) on chromosome 9p21. Recent evidence implicates the CDKN2A/B locus as a causal candidate for developing type 2 diabetes mellitus (T2D). However, aggregate published information to date regarding the specifics of the statistical association between T2D and the genetic variants in the ANRIL region of the CDKN2A/B locus remains equivocal and ambiguous. To clarify this discrepancy, we performed a meta-analysis based on the genotype prevalence and allele frequency of the rs564398 polymorphism (T > C) in ANRIL gene in multiple ethnic populations. The main goal of this work was to conduct a systematic review with a meta-analysis of published data between 2007 and 2018 to determine whether the rs564398 polymorphism of ANRIL gene plays a potential role in predisposition to T2D, also to evaluate the strength, accuracy, and features of this association. We have systematically reviewed studies from databases published between 1990 and 2021. A total of 202 articles were collected, of which only 13 studies from 9 articles (including 13,510 cases and 18,231 controls) met the inclusion criteria and were selected for the statistical meta-analysis. In the present meta-analysis, we have investigated the potential associations between the selected SNP rs564398 and the predisposition to develop T2D, by conducting replicated analysis of already analyzed studies looked for this association, and expand our results by adding new articles published after 2012 and have not been reviewed in a previous meta-analysis, to form our own conclusion about the nature of this association. In contrast to other studies of the locus, we emphasized the differences of risk alleles and genotype influence among different ethnic groups. Ourmeta-analysis indicated that rs564398 [(OR 1.01, 95% CI [0.92, 1.12], P = 0.79) in the dominant model/ [(OR 1.03, 95% CI [0.91, 1.17], P = 0.64) in the recessive model/[(OR 1.00, 95% CI [0.91, 1.09], P = 0.93) in the additive (TC Vs. TT) model]/[(OR 1.00, 95% CI [0.92, 1.08], P = 0.96) in the additive (TC Vs. CC) model]/[(OR 1.02, 95% CI [0.94, 1.11], P = 0.61) in the allelic (C Vs. T) model] is not associated with the development of T2D overall. However, results also revealed slight association in some populations of the included studies. Although our results indicated a lack of association, more extensive studies with larger sample sizes and mixed ethnic groups are necessary to provide a more reliable estimation to confirm the association between rs564398 and T2D. Defining a putative molecular mechanism of rs564398 influence in the pathophysiology of T2D appears warranted.