scholarly journals Variable DNA methylation of aging-related genes is associated with male COPD

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Xizi Du ◽  
Lin Yuan ◽  
Mengping Wu ◽  
Meichao Men ◽  
Ruoxi He ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Mrna Expression ◽  
Differentially Expressed Genes ◽  
Peripheral Blood ◽  
Methylation Level ◽  
Forced Expiratory Volume ◽  
Differentially Expressed ◽  
Control Group ◽  
Cpg Sites ◽  
Copd Patients

Abstract Background Chronic obstructive pulmonary disease (COPD) is a chronic lung inflammatory disease which has a close relationship with aging. Genome-wide analysis reveals that DNA methylation markers vary obviously with age. DNA methylation variations in peripheral blood have the potential to be biomarkers for COPD. However, the specific DNA methylation of aging-related genes in the peripheral blood of COPD patients remains largely unknown. Methods Firstly, 9 aging-related differentially expressed genes (DEGs) in COPD patients were screened out from the 25 aging-related genes profile through a comprehensive screening strategy. Secondly, qPCR and multiple targeted bisulfite enrichment sequencing (MethTarget) were used to detect the mRNA level and DNA methylation level of the 9 differentially expressed genes in the peripheral blood of 60 control subjects and 45 COPD patients. The candidate functional CpG sites were selected on the basis of the regulation ability of the target gene expression. Thirdly, the correlation was evaluated between the DNA methylation level of the key CpG sites and the clinical parameters of COPD patients, including forced expiratory volume in one second (FEV1), forced expiratory volume in one second as percentage of predicted volume (FEV1%), forced expiratory volume/ forced vital capacity (FEV/FVC), modified British medical research council (mMRC) score, acute exacerbation frequency and the situation of frequent of acute aggravation (CAT) score. Lastly, differentially methylated CpG sites unrelated to smoking were also determined in COPD patients. Results Of the 9 differentially expressed aging-related genes, the mRNA expression of 8 genes were detected to be significantly down-regulated in COPD group, compared with control group. Meanwhile, the methylated level of all aging-related genes was changed in COPD group containing 219 COPD-related CpG sites in total. Notably, 27 CpG sites of FOXO3 gene showed a lower False Discovery Rate (FDR) and higher methylation difference values. Also, some variable DNA methylation is associated with the severity of COPD. Additionally, of the 219 COPD-related CpG sites, 147 CpG sites were not related to smoking. Conclusion These results identified that the mRNA expression and DNA methylation level of aging-related genes were changed in male COPD patients, which provides a molecular link between aging and COPD. The identified CpG markers are associated with the severity of COPD and provide new insights into the prediction and identification of COPD.

Genetic analysis of DNA methylation in dyslipidemia: a case-control study

2020 ◽  
Author(s):  
Yi-Tong Ma ◽  
Shuai Liu ◽  
Yang Li ◽  
Xian Wei ◽  
Dilare Adi ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Methylation Level ◽  
Case Control Study ◽  
Case Control ◽  
Control Group ◽  
Cpg Sites ◽  
Heart Center ◽  
Medical University ◽  
The Relationship ◽  
Control Study

Abstract In our previous study, we explored the relationship between TBL2 gene DNA methylation and high-low-density lipoproteinemia (Hyper-LDL). However, Hyper-LDL is only one type of dyslipidemia. In order to expand the scope of clinical application, we explored the correlation between DNA methylation of genes related to lipid metabolism and dyslipidemia in this study. This study is a case-control study. A total of 180 samples were included in this study from the Heart Center of the First Affiliated Hospital of Xinjiang Medical University. The BSAS method was used to detect the DNA methylation levels and haplotypes of AMFR, FBXW7, INSIG1, INSIG2, MBTPS1 and GRINA genes. A total of 259 CpG sites and 14 regions were detected. The study found that a total of 24 CpG sites DNA methylation and 20 haplotypes were statistically different. The GRINA gene DNA methylation level in the dyslipidemia group was higher than that in the control group (2.68 vs 2.36, p = 0.04). ttttttttttttcttttttttttt is significant methylation haplotype of GRINA (p=0.017). Through logistics analysis, it is found that GRINA gene DNA methylation is an independent risk factor for dyslipidemia, and the increase of GRINA gene DNA methylation level will increase the prevalence of dyslipidemia.

scholarly journals Deoxyribonucleic acid methylation in the enhancer region of the CDKN2A/2B and CDKN2B-AS1 genes in blood vessels and cells in patients with carotid atherosclerosis

2020 ◽  
Vol 25 (10) ◽  
pp. 4060
Author(s):  
Yu. A. Koroleva ◽  
A. V. Markov ◽  
I. A. Goncharova ◽  
A. A. Sleptsov ◽  
N. P. Babushkina ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Peripheral Blood ◽  
Methylation Level ◽  
Deoxyribonucleic Acid ◽  
Healthy Individuals ◽  
Peripheral Blood Leukocytes ◽  
Blood Leukocytes ◽  
Blood Samples ◽  
Cpg Sites ◽  
Atherosclerotic Lesions

Aim. Comparative analysis of the deoxyribonucleic acid (DNA) methylation level in the enhancer region of the CDKN2A/2B and CDKN2B-AS1 genes (9p21.3 locus) in vessels with/without atherosclerotic lesions, as well as in leukocytes of patients with clinically relevant carotid artery (CA) atherosclerosis and healthy individuals.Material and methods. The group of patients with clinically relevant atherosclerosis included 22 individuals with severe stenosis (>80%) of CA. Samples of atherosclerotic plaques, presenting CA regions, and great saphenous veins, as well as peripheral blood samples (leukocytes) were obtained from patients. The control group consisted of 14 individuals with the mild CA stenosis (£24%) and without hemodynamically relevant changes; peripheral blood samples were obtained from each of them. DNA methylation level was assessed by targeted bisulfite sequencing of amplicons.Results. The tissue-specific methylation of 31 CpG-site in the CDKN2A/2B and CDKN2B-AS1 gene enhancer was established: the vascular tissues significantly differed from the peripheral blood leukocytes. At the same time, there was an increase in the methylation level of both certain CpG sites and whole analyzed CA region affected by atherosclerosis (48,6 [34,8; 62,0]%), compared with intact vessels, both arteries (25,2 [23,1; 41,60]%, p=0,0001) and veins (35,0 [31,6; 40,0]%, p=0,0039). Patients had lower methylation levels in all CpG sites in blood leukocytes compared to blood vessel samples (8,7 [6,1; 9,7]%; p<0,05). At the same time, the level of DNA methylation in the blood leukocytes of atherosclerotic patients does not differ from that in healthy individuals (9,3 [8,3; 13,6]%; p>0,8).Conclusion. In the present study, the relationship between an increase in the DNA methylation in the enhancer of the CDKN2A/2B and CDKN2B-AS1 genes in CA and their atherosclerotic lesions was revealed, as well as the tissue-specific DNA methylation between vessels and peripheral blood leukocytes.

scholarly journals Aberrant Hypermethylation of Aldehyde Dehydrogenase 2 Promoter Upstream Sequence in Rats with Experimental Myocardial Infarction

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Peng Wang ◽  
Cheng Shen ◽  
Lei Diao ◽  
Zhiyin Yang ◽  
Fan Fan ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Dna Methylation ◽  
Mrna Expression ◽  
Aldehyde Dehydrogenase ◽  
Methylation Level ◽  
Sham Group ◽  
Core Promoter ◽  
Upstream Sequence ◽  
Aldehyde Dehydrogenase 2 ◽  
Cpg Sites

Background. Aldehyde dehydrogenase 2 (ALDH2) plays a crucial role in myocardial protection against ischemia. Downregulation of ALDH2 was evidenced after myocardial infarction and the underlying mechanism is not fully understood. DNA methylation can regulate gene transcription in epigenetic level. We thus hypothesized that DNA methylation may affect ALDH2 expression in myocardial infarction (MI).Methods. MI was induced in Sprague-Dawley rats. MI border zone tissues were harvested at 1st week, 2nd week, and 3rd week after MI. Bisulfite sequencing PCR (BSP) was performed to detect the methylation levels of ALDH2 core promoter. Sequenom MassARRAY platform (MassARRAY) was used to examine the methylation levels of ALDH2 promoter upstream sequence. ALDH2 protein and mRNA expression were assayed by Western blot and real-time PCR, respectively.Results. Compared with Sham group, ALDH2 protein and mRNA expression of MI groups was significantly downregulated. Compared with Sham group, DNA methylation level of CpG sites in ALDH2 promoter upstream sequence was significantly higher in MI groups in a time-dependent manner (CpG1, CpG2, and CpG7,P<0.01). DNA methylation did not affect ALDH2 core promoter sequence during the progress of MI. No significant difference was detected in DNA methylation level of ALDH2 promoter upstream sequence among MI groups.Conclusion. Aberrant hypermethylation of CpG sites in ALDH2 promoter upstream sequence is associated with myocardial ischemia injury and may partly result in ALDH2 downregulation after MI.

scholarly journals Transcriptional and Epigenetic Changes Influencing Skeletal Muscle Metabolism in Women With Polycystic Ovary Syndrome

2018 ◽  
Vol 103 (12) ◽  
pp. 4465-4477 ◽  
Author(s):  
Emma Nilsson ◽  
Anna Benrick ◽  
Milana Kokosar ◽  
Anna Krook ◽  
Eva Lindgren ◽  
...  
Keyword(s):  
Gene Expression ◽  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Dna Methylation ◽  
Polycystic Ovary Syndrome ◽  
Mrna Expression ◽  
Polycystic Ovary ◽  
Differentially Expressed ◽  
Ovary Syndrome ◽  
Cpg Sites

Abstract Context Insulin resistance in skeletal muscle is a major risk factor for the development of type 2 diabetes in women with polycystic ovary syndrome (PCOS). Despite this, the mechanisms underlying insulin resistance in PCOS are largely unknown. Objective To investigate the genome-wide DNA methylation and gene expression patterns in skeletal muscle from women with PCOS and controls and relate them to phenotypic variations. Design/Participants In a case-control study, skeletal muscle biopsies from women with PCOS (n = 17) and age-, weight-, and body mass index‒matched controls (n = 14) were analyzed by array-based DNA methylation and mRNA expression profiling. Results Eighty-five unique transcripts were differentially expressed in muscle from women with PCOS vs controls, including DYRK1A, SYNPO2, SCP2, and NAMPT. Furthermore, women with PCOS had reduced expression of genes involved in immune system pathways. Two CpG sites showed differential DNA methylation after correction for multiple testing. However, an mRNA expression of ∼30% of the differentially expressed genes correlated with DNA methylation levels of CpG sites in or near the gene. Functional follow-up studies demonstrated that KLF10 is under transcriptional control of insulin, where insulin promotes glycogen accumulation in myotubes of human muscle cells. Testosterone downregulates the expression levels of COL1A1 and MAP2K6. Conclusion PCOS is associated with aberrant skeletal muscle gene expression with dysregulated pathways. Furthermore, we identified specific changes in muscle DNA methylation that may affect gene expression. This study showed that women with PCOS have epigenetic and transcriptional changes in skeletal muscle that, in part, can explain the metabolic abnormalities seen in these women.

scholarly journals POS0361 DNA METHYLATION SIGNATURES CHARACTERIZE PSORIASIS AND PSORIATIC ARTHRITIS IN MONOZYGOTIC TWINS DISCORDANT FOR THE DISEASE

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 410.3-411
Author(s):  
M. Vecellio ◽  
A. Ceribelli ◽  
E. Paraboschi ◽  
N. Isailovic ◽  
F. Motta ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Psoriatic Arthritis ◽  
Mrna Expression ◽  
Peripheral Blood ◽  
Methylation Level ◽  
Methylation Profile ◽  
Psoriatic Disease ◽  
Genome Wide ◽  
Dna Methylation Profile ◽  
Mz Twins

Background:Psoriatic disease is a chronic inflammatory disorder spanning from skin disease (psoriasis) to psoriatic arthritis (PsA). The genetic background is insufficient to explain disease onset as illustrated by not very informative Genome Wide Association Studies and monozygotic (MZ) twin studies recently performed. It is strongly assumed that epigenetics may contribute to disease susceptibility modulating gene expression. DNA methylation has been found involved in several autoimmune inflammatory rheumatic diseases. Here we have analysed the DNA methylation profile of a selected cohort of MZ twins discordant for psoriasis/PsA.Objectives:To identify the methylome associated with psoriasis and PsA in the peripheral blood of MZ twins discordant for these conditions.Methods:Peripheral blood from 7 couples of MZ twins discordant for psoriatic disease was collected and DNA extracted for a genome-wide evaluation of the DNA methylation profile, with the Infinium MethylationEPIC BeadChip. Minfi and the packages of the Bioconductor were used to analyse the data obtained. Quality control and exclusion criteria were applied to the raw data having a final number of 762.451 probes, which accounts for 88% of the total.Results:The approach first identified 2564 differentially methylated positions (DMPs; *p<0.005) with 19 genes potentially affected (with at least two DMPs within 1 kb of distance), including SMAD3 and SMARCA4/BRG1 involved in the Interferon and TGFβ pathways. Gene Ontology (GO) analysis of DMP-associated genes showed a significative enrichment (*p<0.005) in transcription factor binding, transcription corepressor and transcription coactivator activity, SMAD binding and histone -lysine-N-methyltransferase activity. To further validate the results, 5’-methylcytosine immunoprecipitation (MedIP) followed by Real Time PCR was performed to assess the methylation level of SMAD3 and SMARCA4/BRG1 promoters in the same cohort of MZ twins. We found significantly DNA methylation enrichment in SMARCA4/BRG1 promoter in psoriatic disease twins (p<0.05). SMAD3 and SMARCA4/BRG1 mRNA expression was also assessed to evaluate any inverse correlation with promoter methylation level, on the MZ cohort used for the EPIC array (n=4) and on a cohort of PsA/Ps patients (n=8) and appropriate healthy controls (n=3). Reduced mRNA expression (p<0.05) was demonstrated for SMARCA4/BRG1 (n=4). Conversely, no changes were found for SMAD3.Conclusion:We report the first DNA methylation approach in MZ twins discordant for psoriatic disease. We believe that the observed changes in SMAD3 and SMARCA/BRG1 genes may suggest an epigenetic imbalance of chromatin remodelling factors involved in inflammation pathways with a potential role in PsA/psoriasis immunopathogenesis.Disclosure of Interests:None declared

scholarly journals PSVII-2 Differentially expressed genes and their biological function in skeletal muscle of calves born from cows with or without protein supplementation during mid-gestation

2020 ◽  
Vol 98 (Supplement_3) ◽  
pp. 165-166
Author(s):  
Elisa B Carvalho ◽  
Letícia P Sanglard ◽  
Karolina B Nascimento ◽  
Javier M Meneses ◽  
Daniel R Casagrande ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Differentially Expressed Genes ◽  
Muscle Development ◽  
Negative Binomial ◽  
Muscle Protein ◽  
Basal Diet ◽  
Protein Supplementation ◽  
Differentially Expressed ◽  
Control Group ◽  
Q Value

Abstract Gestating cows have an increased nutrient demand to meet the needs of developing the fetus and the mid-gestation is a critical period for the fetal skeletal muscle development. The aim of this study was to evaluate the skeletal muscle transcriptome in the progeny as a function of the maternal protein nutrition during mid-gestation. Eleven Tabapuã cows and their male calves were used in this study. In the first third of gestation (0 to 100 days of gestation; dg), all cows were kept on pasture. From 100 to 200 dg, the control group (CTRL; 7 animals) received a basal diet achieving 5.5% crude protein (CP), whereas the supplemented group (SUPPL; 4 animals) received a basal diet plus protein supplementation (40% CP). After 200 dg, all animals received the same diet. Weaning was performed at 205 ± 7.5 days of age and animals were kept on pasture until reaching 240 days of age, when they were transferred to a feedlot. Muscle samples were collected at 260 days of age and RNA was extracted for RNA-seq analysis. Gene expression data was analyzed with a negative binomial model to identify (q-value ≤ 0.05) differentially expressed genes (DEG) between treatments. A total of 716 DEG were identified (289 DEG up-regulated and 427 down-regulated in SUPPL group; q-value ≤ 0.05). From the 10 most significant down-regulated DEG in the SUPPL group, two genes associated with apoptotic process were identified: MAPK8IP1 and GRINA, with log2 Fold-Changes (log2FC) of 1.04 and 0.49, respectively. From the 10 most significant up-regulated DEG in the SUPPL group, mTOR was identified, with log2FC=0.31. This is a well-known gene involved in muscle protein synthesis. In conclusion, maternal protein supplementation during mid-gestation affects the expression of genes related to energy metabolism and muscle development, which can lead to long-term impacts on production efficiency.

scholarly journals Gene expression and DNA methylation analyses suggest that two immune related genes are prognostic factors of colorectal cancer

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Xiao-Liang Xing ◽  
Zhi-Yong Yao ◽  
Chaoqun Xing ◽  
Zhi Huang ◽  
Jing Peng ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Risk Assessment ◽  
Dna Methylation ◽  
Differentially Expressed Genes ◽  
Risk Score ◽  
Immune Cells ◽  
Assessment Model ◽  
Differentially Expressed ◽  
Risk Assessment Model

Abstract Background Colorectal cancer (CRC) is the second most prevalent cancer, as it accounts for approximately 10% of all annually diagnosed cancers. Studies have indicated that DNA methylation is involved in cancer genesis. The purpose of this study was to investigate the relationships among DNA methylation, gene expression and the tumor-immune microenvironment of CRC, and finally, to identify potential key genes related to immune cell infiltration in CRC. Methods In the present study, we used the ChAMP and DESeq2 packages, correlation analyses, and Cox regression analyses to identify immune-related differentially expressed genes (IR-DEGs) that were correlated with aberrant methylation and to construct a risk assessment model. Results Finally, we found that HSPA1A expression and CCRL2 expression were positively and negatively associated with the risk score of CRC, respectively. Patients in the high-risk group were more positively correlated with some types of tumor-infiltrating immune cells, whereas they were negatively correlated with other tumor-infiltrating immune cells. After the patients were regrouped according to the median risk score, we could more effectively distinguish them based on survival outcome, clinicopathological characteristics, specific tumor-immune infiltration status and highly expressed immune-related biomarkers. Conclusion This study suggested that the risk assessment model constructed by pairing immune-related differentially expressed genes correlated with aberrant DNA methylation could predict the outcome of CRC patients and might help to identify those patients who could benefit from antitumor immunotherapy.

scholarly journals RNA-Seq Transcriptome Analysis of Peripheral Blood From Cattle Infected With Mycobacterium bovis Across an Experimental Time Course

2021 ◽  
Vol 8 ◽  
Author(s):  
Kirsten E. McLoughlin ◽  
Carolina N. Correia ◽  
John A. Browne ◽  
David A. Magee ◽  
Nicolas C. Nalpas ◽  
...  
Keyword(s):  
Differentially Expressed Genes ◽  
Mycobacterium Bovis ◽  
Peripheral Blood ◽  
Post Infection ◽  
Time Course ◽  
De Novo ◽  
Differentially Expressed Gene ◽  
Differentially Expressed ◽  
Infection Time ◽  
Time Point

Bovine tuberculosis, caused by infection with members of the Mycobacterium tuberculosis complex, particularly Mycobacterium bovis, is a major endemic disease affecting cattle populations worldwide, despite the implementation of stringent surveillance and control programs in many countries. The development of high-throughput functional genomics technologies, including RNA sequencing, has enabled detailed analysis of the host transcriptome to M. bovis infection, particularly at the macrophage and peripheral blood level. In the present study, we have analysed the transcriptome of bovine whole peripheral blood samples collected at −1 week pre-infection and +1, +2, +6, +10, and +12 weeks post-infection time points. Differentially expressed genes were catalogued and evaluated at each post-infection time point relative to the −1 week pre-infection time point and used for the identification of putative candidate host transcriptional biomarkers for M. bovis infection. Differentially expressed gene sets were also used for examination of cellular pathways associated with the host response to M. bovis infection, construction of de novo gene interaction networks enriched for host differentially expressed genes, and time-series analyses to identify functionally important groups of genes displaying similar patterns of expression across the infection time course. A notable outcome of these analyses was identification of a 19-gene transcriptional biosignature of infection consisting of genes increased in expression across the time course from +1 week to +12 weeks post-infection.

scholarly journals Genomic Expression Profiling of Colorectal Cancer in Silico

2021 ◽  
Author(s):  
Feifei Liu ◽  
Yu Wang ◽  
Wenxue Li ◽  
Diancheng Li ◽  
Yuwei Xin ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Survival Analysis ◽  
Mrna Expression ◽  
Differentially Expressed Genes ◽  
Expression Profiles ◽  
Functional Enrichment ◽  
Differentially Expressed ◽  
Analysis Tool ◽  
Hub Genes ◽  
Normal Tissues

Abstract Background: Colorectal cancer (CRC) is one of the most common malignancies of the digestive system; the progression and prognosis of which are affected by a complicated network of genes and pathways. The aim of this study was to identify potential hub genes associated with the progression and prognosis of colorectal cancer (CRC).Methods: We obtained gene expression profiles from GEO database to search differentially expressed genes (DEGs) between CRC tissues and normal tissue. Subsequently, we conducted a functional enrichment analysis, generated a protein–protein interaction (PPI) network to identify the hub genes, and analyzed the expression validation of the hub genes. Kaplan–Meier plotter survival analysis tool was performed to evaluate the prognostic value of hub genes expression in CRC patients.Results: A total of 370 samples, involving CRC and normal tissues were enrolled in this article. 283 differentially expressed genes (DEGs), including 62 upregulated genes and 221 downregulated genes between CRC and normal tissues were selected. We finally filtered out 6 hub genes, including INSL5, MTIM, GCG, SPP1, HSD11B2, and MAOB. In the database of TCGA-COAD, the mRNA expression of INSL5, MT1M, HSD11B2, MAOB in tumor is lower than that in normal; the mRNA expression of SPP1 in tumor is higher than that in normal. In the HPA database, the expression of INSL5, GCG, HSD11B2, MAOB in tumor is lower than that in normal tissues; the expression of SPP1 in the tumor is higher than that in normal tissues. Survival analysis revealed that INSL5, GCG, SPP1 and MT1M may serve as prognostic biomarkers in CRC. Conclusions: We screened out six hub genes to predict the occurrence and prognosis of patients with CRC using bioinformatics methods, which may provide new targets and ideas for diagnosis, prognosis and individualized treatment for CRC.

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