Meta Gene最新文献

Schizophrenia is a chronic serious neuropsychiatric disorder with a prevalence of 1% worldwide. Neurogenic locus NOTCH homolog protein 4 known as the NOTCH4 gene is located on chromosome 6p. NOTCH4 protein is a transmembrane protein that plays a major role in cell signaling pathways and cell differentiation. NOTCH4 SNP rs367398 is located in the gene's largest intron, intron 18, which is an area of known importance in transcriptional regulation and may be related to schizophrenia. Although many studies have shown the association of NOTCH4 polymorphism with schizophrenia, the exact molecular mechanism behind this still unknown. This study was aimed to determine the frequency of NOTCH4 rs367398 & rs387071 polymorphism and its association with schizophrenia. In total, 150 schizophrenia patients and 100 healthy controls were recruited from psychiatry department after obtaining written informed consent. NOTCH4 polymorphism was genotyped using PCR-RFLP. Positive and Negative Syndrome Scale (PANSS) and Global assessment of functioning (GAF) were used to assess the severity of schizophrenia. Both the NOTCH4 rs367398 & rs387071 genotypes were significantly associated with schizophrenia. On gender based analysis, the rs387071 was significantly associated with schizophrenia in males and whereas the rs367398 is associated with females of the study group. Further, the haplotype analysis has also supported the association of NOTCH4 locus with schizophrenia (Global haplotype association p = 0.021). The findings of the study suggest that the NOTCH4 polymorphism is significantly associated with schizophrenia in Indian population. These SNPs might also have an important role in the symptomatology of the disease.

DISC1 regulates signalling pathways which are involved in neuronal development, brain maturation like neuronal proliferation and processes involved in central nervous system development. The DISC1 gene is one of the potential candidate gene involved in Schizophrenia risk. In the present study, we performed case-control association study using TaqMan based chemistry in which a total of 382 individuals, 152 Schizophrenia patients and 230 healthy controls were genotyped to explore the association of rs3738401 and rs16854954 of DISC1 gene with susceptibility to Schizophrenia risk in North Indian population of Jammu region. The findings from the study revealed that rs3738401 was significantly associated with Schizophrenia and the G allele of rs3738401 is associated with increased risk for the disorder (OR = 1.66; [1.22–2.24 at 95%CI] P = 0.001) whereas other variant rs16854954 of DISC1 gene was not found to be associated with the disease(OR = 0.96, [0.71–1.30 at 95% CI] P = 0.75). The present study offers an important evidence on the genetic cause of DISC1 gene in North Indian population and further strengthens the GWAS findings on the role of DISC1 in schizophrenia risk. This study provides the holistic view about the Schizophrenia in Jammu region, North Indian population and it can be a hallmark if verified on a very large sample size (cohort).

Background

The DNA methyltransferase 3B (DNMT3B) play a significant role for methylating the intragenic regions of active genes. Findings of previous studies suggested an association between the DNMT3b 579G>T single-nucleotide polymorphism (SNP) and susceptibility to various tumors. However, limited studies have examined the association of DNMT3B 579G>T polymorphism with gastric cancer risk (GC), and their results are contradictory. This meta-analysis was carried out in order to assess this association.

Methodology

We conducted a thorough literature search using in PubMed, Science Direct and Google Scholar databases for relevant studies published up to January 14, 2021. A total of 5 studies were identified and included in this work. The pooled odd rates (ORs) with 95%CIs were estimated using a fixed-effect or random-effect model to take into account the heterogeneity between studies.

Results

We found no impact of DNMT3B 579G>T polymorphism on gastric cancer under all genetic models: Allelic model [G vs T, odds ratio (OR) = 0.79, 95% confidence of interval (CI): 0.55–1.13, p = 0.20], recessive model [GG vs GT + TT, OR = 0.96, 95% CI: 0.63–1.46, p = 0.86], dominant model [GG + GT vs TT, OR = 0.72, 95% CI: 0.47–1.10, p = 0.13], heterozygous model [GT vs TT, OR = 0.70, 95% CI: 0.45–1.08, p = 0.11] and homozygous model [GT vs TT, OR = 0.72, 95% CI: 0.44–1.17, p = 0.18], homozygous, OR: 0.72, 95% CI = 0.44–1.17, p = 0.18).

Conclusion

Our results indicated that DNMT3B 579G>T is not associated with GC, and it may not be used as a stratification marker to predict susceptibility.

Matrix metalloproteinases - 2 (MMP2) protein stimulates multiple processes involving the nervous system, vascularization, and metastasis. Mutations in MMP2 is linked to Winchester and Nodulosis-Arthropathy-Osteolysis (NAO) syndromes. In this extensive investigation, we performed a computational analysis of 114 missense Single Nucleotide Polymorphisms (SNPs) of MMP2 protein using various in-silico algorithms. A total of 21 highly deleterious and pathogenic missense SNPs (T86K, R146H, A167T, G216E, R252P, R252L D326V, D326Y, G346S, G367S, R368L, S396R, A408P, R482C, P517L, A522E, E525K, Y543C, Y552S, K579M, M598T) were identified that probably could alter the structural and functional configuration of MMP2 gene. Moreover, conservation analysis, protein stability, TM-score and RMSD calculation, protein structure prediction and superimposition, ligand binding site prediction, protein-protein interaction, protein-ligand, and protein-protein docking studies were carried out. ConSurf analysis showed seventeen missense variants in the highly conserved regions, which were predicted as highly deleterious and pathogenic by eight in-silico platforms. Furthermore, G367S and K579M showed a greater impact on stability, structural alterations, protein-ligand and protein-protein interactions. This study will help in developing target-dependent medication for diseases and could enhance the understanding of the significance of uncharacterized missense SNPs and their interrelation with the disease. This study also contemplates the computational perception into the high-risk missense SNPs on protein structural and functional configuration.

Purpose

Ghrelin is found as an endogenous ligand for growth hormone secretagogue receptor (GHSR). Several studies have reported an association between plasma ghrelin and GHRL-single nucleotide polymorphism, namely the Leu72Met polymorphism, with Body mass Index, type 2 diabetes mellitus, and insulin resistance. The role of gene variant of GHRL Leu72Met in obesity is still unclear. The aim of the present study was to examine the associations of Leu72Met with ghrelin levels, insulin secretion, and obesity among Javanese subjects.

Materials and methods

All subjects were measured with anthropometry, and fasting blood glucose was measured by the glucose oxidase-phenol and 4 aminophenazone method. Plasma insulin and ghrelin were measured using ELISA. Insulin secretion was calculated using HOMA analysis. The Leu72Met genetic variant of the ghrelin gene was screened using PCR-RFLP.

Results

Plasma ghrelin concentrations were lower in the obese group than the lean group (P < 0.05). Fasting plasma ghrelin was negatively correlated with body mass index and insulin secretion. Subjects with the Met72 allele carried a higher risk of obesity than the subjects with the Leu72 allele (OR = 4.928 [95% CI = 2.424–10.01]).

Conclusion

The conclusion of this study is Leu72Met polymorphisms increases the risk of obesity in Javanese ethnicity, but this polymorphism does not play a role in plasma ghrelin secretion and plasma insulin secretion.

Purpose

Study aim to investigate the possible role of Fok I VDR polymorphism in TB risk assessment.

Methods

To investigate the role of Fok I VDR polymorphism in TB risk assessment, we collected a blood sample from 106 healthy individuals including both gender. The genomic DNA was isolated and the VDR gene was amplified using gene-specific primers using polymerase chain reaction. The Genotyping of the Fok I polymorphism was performed using Fok I restriction enzyme. The distribution of genotype frequencies of VDR gene polymorphisms was calculated using Hardy-Weinberg equilibrium calculator.

Results

In the present investigation, the VDR gene was amplified with an undigested DNA band of 265 bp as FF homozygote. Additionally, 169 bp and 96 bp as ff homozygote and three bands ((265 bp, 169 bp, and 96 bp) were observed in the heterozygote. As per our finding, we report a significantly low frequency of susceptible genotypes in Ff (27.4%) and ff (6.6%) compared to average frequency Ff = 41.80% and ff = 8.25% of India. We also reported here the low frequency of mutant allele f in India's central part, i.e., Bhopal division, Madhya Pradesh. Considering our finding, the mutant allele's low frequency in central India, Madhya Pradesh, shows a negligible contribution of Fok I VDR polymorphism in TB prevalence.

Conclusions

In a comparative analysis with the Northern and Southern India population based on previous reports, the involvement of FoK I polymorphism in the VDR gene was non-significant in Central India. All the studied populations were found in Hardy-Weinberg equilibrium except North India for the Fok1 VDR genotypes.

Background

Long-term administration of metformin in Type 2 Diabetes mellitus (T2DM), interferes with the absorption of vitamin B12 resulting in deficiency. Low levels of vitamin B12 are associated with cardiovascular morbidity and mortality in T2DM patients. Several genetic variants are associated with vitamin B12 deficiency; one among them is Methylene Tetrahydrofolate reductase (MTHFR). We analyzed MTHFR (rs180133) polymorphism and its association with metformin induced vitamin B12 deficiency in T2DM patients.

Methods

Three hundred T2DM patients were included. For the study and they were screened for vitamin B12 deficiency markers – Methyl malonic acid (MMA), Homocysteine (Hcy) and high sensitive C reactive protein (hsCRP). Genetic variant was analyzed by ARMS-PCR method. Data was analyzed with various statistical tools like ROC, Odds ratio and Likelihood ratio.

Results

There is significant reduction in folic acid and vitamin B12 in metformin users. HsCRP, Hcy and MMA are significantly increased with P < 0.001 in patients with metformin induced B12 deficiency. T allele in MTHFR (T allele ORs =2.1, TT genotype =3.6) showed risk of vitamin B12 deficiency in T2DM patients on metformin therapy. MTHFR gene polymorphism of TT genotype had a Likelihood ratio (LR) of 2.46 for folic acid, 2.77 for MMA and 3.38 for Hcy.

Conclusion

We found an association between MTHFR rs180133, 677C > T and vitamin B12 status in T2DM patients on metformin therapy. Folic acid, MMA and Hcy were found to have high specificity in concordance with MTHFR which showed to be a good predictor for vitamin B12 deficiency in T2DM patients on metformin therapy.

Background

Previous studies suggested, variations in the IL28B gene can serve as predictors of sustained and rapid virological responses (SVR and RVR) in the treatment of HCV with pegylated interferon and ribavirin (pegINF-RBV) among HCV-HIV co-infected patients. Here, we explored the correlation between IL28B variants (rs12979860, rs8099917 and rs12980275) and treatment response for HCV among co-infected individuals using meta-analysis.

Methods

Relevant studies were retrieved from PubMed, EBSCO, ISI Web of Knowledge, Cochrane databases, and the role of IL28B variants on SVR and RVR in co-infected patients treated with pegINF-RBV was evaluated. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by fixed- and random-effects models.

Results

Forty-three studies consisting 3499 patients who achieved SVR/RVR and 4308 non-responders were included in our study. The CC, TT and AA genotypes of IL28B rs12979860, rs8099917 and rs12980275, respectively, were associated with SVR in the recessive model for all HCV genotypes: rs12979860, OR = 3.18 [95% CI (2.66, 3.79)]; P < 0.0001; rs8099917, OR = 3.6`9 [95% CI (2.74, 4.97)]; P < 0.0001; rs12980275, OR = 2.97 [95% CI (2.26, 3.89)]; P < 0.0001. Significant association of rs12979860 CC genotype with RVR was also found: OR = 2.31 [95% CI (1.54, 3.57)]; P < 0.0001. Stratification analysis of HCV genotypes revealed similar trends of association with the rs12979860 CC genotype for HCV-1, HCV-1/4 and HCV-4, but no association was found for HCV-2/3 and HCV-3.

Conclusions

Our meta-analysis suggests that the CC, TT and AA genotypes of IL28B rs12979860, rs8099917 and rs12980275, respectively, are strong predictors for SVR, and the rs12979860 CC genotype has significant RVR predictive value in HCV-HIV co-infected patients treated with pegINF-RBV.

Background

In Ukraine, 3539 patients were diagnosed with ovarian cancer in 2018, and more than half of these cases were lethal. One of the risk factors for ovarian cancer development are the alterations in the breast cancer gene 1 (BRCA1). Among these alterations, the most frequent is the germline mutation 185delAG and the frameshift mutation 4153delA. The frequencies of these mutations were identified earlier (Tsip et al., 2019) in ovarian cancer patients from Ukraine.

Objective

The present study aimed to evaluate the frequency of the mutations 185delAG and 4153delA in the BRCA1 gene in an unselected ovarian cancer patient's cohort from Ukraine.

Materials and methods

We screened 663 ovarian cancer patients diagnosed at different ages by routine allele-specific polymerase chain reaction (PCR) and real-time PCR.

Results

13 cases of two BRCA1 mutations were detected (4 cases of 185delAG and 9 cases of 4153delA).

Conclusions

Out of 663 ovarian cancer patients, 4 cases with 185delAG and 9 cases of 4153delA in the BRCA1 gene were identified, giving a frequency of 2.0 ± 0.5%. Our data shows that the previous mutations screening results in ovarian cancer patients from Ukraine were higher than in the present study.

COVID-19 is a newly emerged viral disease that is currently affecting the whole globe. A variety of therapeutic approaches are underway to block the SARS-CoV-2 virus. Among these methods, siRNAs could be a safe and specific option, as they have been tested against other viruses. siRNAs are a class of inhibitor RNAs that act promisingly as mRNA expression blockers and they can be designed to interfere with viral mRNA to block virus replication. In order to do this, we designed and evaluated the efficacy of six highly specific siRNAs, which target essential viral mRNAs with no predicted human genome off-targets. We observed a significant reduction in the copy number viral mRNAs after treatment with the siRNAs, and are expected to inhibit virus replication. We propose siRNAs as a potential co-therapy for acute SARS-CoV-2 infection.