Meta Gene最新文献

Background

Adams–Oliver syndrome (AOS [MIM 100300]) is a rare, multiple malformation syndrome commonly characterized by scalp aplasia cutis congenita (ACC) and transverse terminal limb defects (TTLD). Brain abnormalities and heart defects are also present in most patients. Both autosomal-dominant and autosomal-recessive inheritance of the disease have been observed. To date, six causative genes have been identified: ARHGAP31, DOCK6, EOGT, RBPJ, NOTCH1, and DLL4. Autosomal-recessive mutations are mostly associated with DOCK6 (MIM: 614219) and EOGT (MIM: 615297), while mutations in ARHGAP31 (MIM: 100300), RBPJ (MIM: 614814), NOTCH1 (MIM: 616028), and DLL4 (MIM: 616589) have been linked to autosomal-dominant inheritance.

Case

We report a case of AOS caused by DOCK6 mutations (c.3190_3191del and c.4491 + 1G > T), showing no signs of scalp ACC or TTLD, but with bilateral ventricular dilation and ophthalmic abnormalities. Results of whole-exome high-throughput sequencing were analyzed using a combination of pathogenicity prediction algorithms, query of variant databases, and review of the literature. Candidate gene variation sites were identified for pedigree verification.

Conclusions

The correlation between the genotype and phenotype of AOS has great variability, and the specific pathogenesis of AOS remains to be further studied.

The studies have reported several additional non-syndromic cleft lip/palate (NSCL/P) susceptibility loci. This systematic review and meta-analysis aimed to evaluate the linkage and association of PAX7 polymorphisms with the NSCL/P risk. A comprehensive search was conducted in the PubMed, Cochrane Library, Web of Science, and Scopus databases until May 15, 2021. The association between PAX7 polymorphisms and NSCL/P susceptibility was analyzed by calculation of the odds ratios (ORs) and 95% confidence intervals (CIs), and the linkage was assessed by the allelic transmission disequilibrium test. Some articles included more than one study (reporting more than one polymorphism). Therefore, nine articles including 13 studies were entered into the meta-analysis. With regard to the association of rs742071 polymorphism with the risk of NSCL/P, the pooled OR was 1.33 for the allelic (P < 0.0001), 1.98 for the homozygous (P = 0.0007), 1.41 for the heterozygous (P = 0.0267), and 1.15 for the dominant (P = 0.2542) models. For the association of PAX7 rs766325 and rs4920520 polymorphisms with the risk of NSCL/P, the pooled OR was 0.96 (P = 0.5571) and 1.14 (P = 0.1020), respectively. In addition, the pooled allelic transmission disequilibrium test for s742071 and rs766325 polymorphisms did not show any allelic linkage between these polymorphisms and susceptibility to NSCL/P. The main results of the present systematic review and meta-analysis showed an association between PAX7 rs742071 polymorphism and NSCL/P susceptibility; but there was no linkage or association with rs766325 and rs4920520 polymorphisms.

Background

What is the etiology of skin tags? What factors are involved in the patho-biochemistry of combined skin tags and internal malignancy? This study aimed to assess the possible linkage between CDH1 gene polymorphisms and skin tags and whether certain CDH1-SNPs are the key to developing internal malignancies in the subjects with skin tags.

Materials and methods

CDH1 polymorphisms were assessed in 164 skin tag subjects and 126 controls. We followed up the subjects with skin tags every six months for 48 months to assess whether anyone developed internal malignancy and if that malignancy was linked to certain CDH1 polymorphism.

Results

CDH1rs13689 genotypes were T/T (1.2% vs 4.8%), T/C (46% vs 60%) and C/C (70.7% vs 47.6%) for the skin tag subjects and the controls, respectively (p < 0.001). The CDH1rs17715799 genotypes were A/A (29.3% vs 50.8%), A/T (56.1% vs 44.4%) and T/T (14.6% vs 4.8%) for the skin tag subjects and the controls, respectively, (p < 0.001). After follow up, six patients with skin tags developed internal malignancies.

Conclusions

CDH1 genetic variants may be incriminated in the process of skin tag formation through epithelial-mesenchymal transition (EMT). Obesity and diabetes mellitus (DM) are substantial risk factors for EMT. Internal malignancy might develop with skin tags, so these patients should be followed up. The mutant CDH1rs13689 and/or rs17715799 may be the key to the presence of combined skin tags and malignancy.

Background

The level of angiotensin-converting enzyme 2 (ACE2) expression in different tissues is essential in the sensitivity, symptoms and consequences of COVID-19 infection. It seems that zinc is involved in the structure of the ACE2 enzyme has been identified; nonetheless, the relationship between ACE2 expression and zinc serum levels in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected patients is still unclear. This study aimed to evaluate the expression of ACE2 in peripheral blood-derived immune cells of COVID-19 patients and its relationship with serum zinc levels.

Methods

Thirty healthy subjects and thirty patients with COVID-19 were enrolled in this study. The COVID-19 infection was confirmed by positive real-time polymerase chain reaction (RT-PCR) and radiological data. Peripheral blood samples were taken from healthy subjects and COVID-19 patients. Whole blood samples were also used to measure ACE2 gene expression by RT-PCR technique. The correlation matrix evaluated the relationship between ACE2 expression, serum zinc levels, and other related variables.

Results

The outcomes showed no considerable alteration in serum zinc levels between patients and the control group. Likewise, the ACE2 gene expression results showed a significant decrease in this receptor's expression in COVID-19 patients compared with the healthy subjects. A significant positive correlation was observed between serum zinc level and ACE2 gene expression in patients with COVID-19.

Conclusion

The immune system seems to reduce the mRNA expression of the ACE2 in the peripheral blood leukocytes following SARS-CoV-2 infection. Moreover, zinc deficiency can make patients more susceptible to SARS-CoV-2 infection.

Background

Non-small cell lung cancer (NSCLC) is the principal subtype of lung cancer. Among all therapeutic options, platinum-based chemotherapy agents, especially Cisplatin, are still commonly used treatment for NSCLC patients. However, developing chemoresistance in NSCLC cells often gives rise to chemotherapy failure. Therefore, more studies are required to shed light on gene interaction and cellular pathways involved in initiating and developing resistance to platinum-based chemotherapy in NSCLC. Hence, it is urgent to find the key genes, microRNA (miRNAs), and potential molecular mechanisms implicated in chemoresistance and present markers to predict response to platinum-based chemotherapy in NSCLC patients.

Methods

The microarray datasets GSE6410, GSE7035, GSE14814, GSE26704, GSE73302 were downloaded from the Gene Expression Omnibus (GEO) database and were analyzed using R software. Functional and pathway enrichment analyses were performed using the Enrich R site. Then, the protein-protein interaction (PPI) network and hub genes were obtained using the Cytoscape software. Further, the miRSystem database was performed to predict the miRNAs regulating the hub genes. Moreover, Cytoscape software and the CytoHubba plugin were used to construct the miRNA-target interaction network and hub modules. Finally, the Kaplan–Meier curve was used to demonstrate the survival curves and assess the association of the genes signature with clinical outcomes.

Results

A total of 142 differentially expressed genes (DEGs) were found. The gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses present the p53 signaling pathway as the most significant pathway.

Besides, from the top ten terms obtained of Biological Process, Molecular Function, and Cellular Component, the first ones, including cholesterol biosynthetic process, the extrinsic component of external side of plasma membrane, cytokine activity, were selected respectively. Based on the PPI network, the ten nodes with the highest degree were screened as hub genes. In addition, from the miRNA–target regulatory network in Cytoscape, ten hub nodes were found. Ultimately, according to Kaplan–Meier curve, BTG2 and TP53I3 with p-value <0.05 were associated with a better prognosis.

Conclusions

In the present study, DEGs, candidate miRNAs, and underlying mechanisms involved in chemoresistance were identified to suggest potential biomarkers to provide new clues for the prediction of response to platinum-based chemotherapy.

Objective

Various reports have examined the contribution of the CTLA4 c.49A > G (rs231775; p.Thr17Ala) gene variant with different cancerous disorders. This meta-analysis was executed to further probe into the involvement of this missense variant with the susceptibility for hepatocellular carcinoma (HCC) and gastric cancer (GC).

Methodology

Following a wide-based scrutinized search of the internet done by three independent researchers for the contribution of the CTLA4 c.49A > G (rs231775; p.Thr17Ala) variant with the cancer risk up to February 2021, only 16 case-control studies were found relevant and usable to the analysis out of 575 total retrieved reports. Multiple genetic models were checked for the proposed association through the computation of the odds ratio (OR) in addition to their 95% confidence intervals (95%CIs). Stratification and regression analysis was also carried out for the analyzed reports based on their geographical distributions, genotyping techniques, source of cancer-free controls, genetic equilibrium within cancer-free controls, and quality score. In addition, trial sequential analysis (TSA) was applied to test for the adequacy of the total sample size.

Results

This meta-analysis has included 4320 HCC and GC patients in conjunction with 6601 cancer-free controls. This work disclosed a significant association for the CTLA4 c.49A > G (rs231775; p.Thr17Ala) variant with HCC among overall subjects tested by the recessive model [OR = 1.235, 95% CI = 1.050–1.453, P-value = 0.011]. Similarly, an elevated risk of GC was noticed associated with this variant within the overall subjects tested by the allelic model [OR = 1.225, 95% CI = 1.070–1.401, P-value = 0.003], and dominant model [OR = 1.352, 95% CI = 1.081–1.691, P-value = 0.008]. Furthermore, the stratification analysis showed a verification of correlation for this variant with HCC in Asian subjects under the recessive model, while the association was observed to be significant with GC in Asian and Caucasian patients under the dominant model. TSA confirmed that this work had significant findings noting that the collective Z-curve spanned the examining borderlines prior to attaining sample size confirming the acceptability of the study sample size.

Conclusion

The CTLA4 c.49A > G (rs231775; p.Thr17Ala) gene variant could be considered as an actual risk factor for the susceptibility of HCC and GC warranting efficient and adequate genetic counseling for this gene variant carriers.

Summary

The mechanisms involved in aneurysmal etiology are complex and only partially understood. Genetic risk factors have already been related to the process of aneurysm rupture. Among the genetic factors, the T-786C and Glu298Asp polymorphisms of the eNOS gene have great clinical relevance, as they can affect the bioavailability of nitric oxide for the cerebrovascular system.

Objective

To evaluate the relationship between eNOS T-786C and Glu298Asp polymorphisms and the aneurysm pathogenesis of patients seen in the Neurosurgery Department of Santa Casa de Belo Horizonte, as well as to compare them with sociodemographic characteristics and risk factors.

Methods

A total of 211 whole blood samples were collected from patients with cerebral aneurysms, 160 with ruptured aneurysms, 51 with unruptured aneurysms and 215 controls. After DNA extraction, genotyping was performed using the PCR-RFLP technique. Allele and genotype frequencies were obtained using the GENEPOP 4.2 software, and statistical analysis was performed using the GraphPad Prism 5.0 program and RStudio version 1.4.

Results

Age, female sex, smoking and small diameter of the aneurysms were associated with aneurysm development and rupture in the study population. The CC genotype of the T-786C polymorphism was associated with unruptured aneurysms with a diameter >12 mm.

Conclusion

Age, female sex and smoking were associated with rupture. This study revealed that the CC mutant genotype of the eNOS gene T-786C polymorphism was associated with unruptured intracranial aneurysms larger than 12 mm in our study population, revealing a new association.

To evaluated the possible correlations of prostate cancer and three coding region polymorphisms (rs 6257, rs6258, rs 6259), & changing repeat of TAAAA in promoter of SHBG gene regarding to concentration of Prostate specific Antigen and SHBG levels. For study purpose, a total of 352 subjects (176 patients and 176 controls) were recruited. The ELISA technique and the RFLP-PCR method were used. Logistic and adjusted regression of genotypes showed that the (TAAAA)n polymorphism in individuals carrying more than five repeats of the five-nucleotide sequence of TAAAA, as well as AA+AG (rs6257) and AA+AG (rs6259), increased the risk of prostate cancer by the chance ratio of 1.622, 2.005, and 2.469, respectively. The studied polymorphisms showed a significant relationship with the stage of the disease and Gleason score. The individuals carrying the mutants were less likely to develop prostate cancer than the ones with wild genotypes. All the genotypes in the cancer group had higher serum levels of tPSA and fPSA than those in the control group. A significant association was observed (except tPSA and fPSA for GT (rs6258) and fPSA for GA (rs6259)). Serum level of SHBG also showed a significant correlation with prostate cancer in genotypes >Panta TAAAA (TAAAA)n, GG (rs6257), TT and TT + CT (rs6258), and GG, AA, and AA+GA (rs6259). These polymorphisms by changing the serum levels SHBG contributed to the incidence of prostate cancer.

Despite increasing burden of autoimmune thyroid disease (AITD) in India, there is paucity of data for the genetic susceptibility in Indian population which represents an important aspect to uncover the genetic factors for the cause or progression of different forms of AITD. It is known that production of auto-antibodies to thyroglobulin (TG) and thyroid peroxidase (TPO) is a characteristic feature of AITD. Production of high titres of auto-antibodies against TG and TPO is one the hallmarks of AITD that often precedes the development of clinical disease. The gene coding for cytotoxic T lymphocyte antigen-4 (CTLA-4) is considered an important candidate gene for susceptibility to AITD and also determines seropositivity. Earlier studies have demonstrated that polymorphic variants in CTLA-4 gene are linked to determine seropositivity. Hence, this study investigates a relationship between CTLA-4 (+49A/G) genotypes and seropositivity to anti-TPO and anti-TG antibodies in AITD patients. A total of 85 Indian participants were included and genotyped for CTLA-4 (+49A/G) single nucleotide polymorphism and further analyzed for seropositivity of TPO and TG auto-antibodies in mean age group of 35.76 ± 12.42 years of both the genders. The TPO seropositivity was reported higher in G allele containing genotypes GG and AG (66.66% and 58%, respectively) compared to AA (44.8%) genotype. Whereas, TG auto-antibodies showed highest seropositivity for genotype AA (55.17%) compared to AG (36%) and GG (16.6%). Higher median titre values were observed for TPO antibodies with GG genotype (1587.461 U/mL). In contrast to this, higher titres of auto-antibodies to TG were observed for individuals with AA genotype (520.746 U/mL). In conclusion, this study demonstrates a relationship between CTLA4 (+49A/G) genotype and seropositivity to thyroid auto antigens TPO and TG in Indian patients with clinical manifestation of Hashimoto's thyroiditis and Graves' disease, two different forms of AITD.

Introduction

Alzheimer's disease (AD), as a neurodegenerative disease, is the most common reason for dementia in the elderly. ATP- binding cassette transporter 1 (ABCA1) is a cell membrane transporter protein which is involved in cholesterol efflux. The aim of this study is to evaluate the correlation between polymorphisms of G/A (rs2230806) in ABCA1 gene with sporadic Alzheimer's disease in the southwest of Iran.

Methods

This case-control study was conducted in 180 subjects, including 100 sporadic AD patients and 80 healthy subjects. Genotypes of all samples were determined using the PCR–restriction fragment length polymorphism (PCR–RFLP) technique.

Results

The analysis of the R219K Polymorphism of ABCA1 gene indicated that there was no significant distinction between AD patients and controls. In this study when groups were stratified by age and sex, results showed that in the control group with less than 75 years, the risk of developing AD was significantly lower than subjects who were older than 75 years (P = 0.019, OR = 0.46, 95% CI = 0.24–0.88). A significant difference was detected in the risk of AD between patient and control in females older than 75 years (P = 0.028).

Conclusion

The results of this study confirm that aging is an important risk factor for AD. Also, it has been found that AD is more prevalent in women compared to men. However, our results do not support the hypothesis that R219K polymorphism in the rs2230806 region of the ABCA1 as a genetic risk factor for developing AD in our study population.