scholarly journals Age-related differences in monocyte DNA methylation and immune function in healthy Kenyan adults and children

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Katherine R. Dobbs ◽  
Paula Embury ◽  
Emmily Koech ◽  
Sidney Ogolla ◽  
Stephen Munga ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Young Adults ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Innate Immune ◽  
Inflammatory Gene Expression ◽  
Cpg Sites ◽  
Age Related ◽  
Adults And Children

Abstract Background Age-related changes in adaptive and innate immune cells have been associated with a decline in effective immunity and chronic, low-grade inflammation. Epigenetic, transcriptional, and functional changes in monocytes occur with aging, though most studies to date have focused on differences between young adults and the elderly in populations with European ancestry; few data exist regarding changes that occur in circulating monocytes during the first few decades of life or in African populations. We analyzed DNA methylation profiles, cytokine production, and inflammatory gene expression profiles in monocytes from young adults and children from western Kenya. Results We identified several hypo- and hyper-methylated CpG sites in monocytes from Kenyan young adults vs. children that replicated findings in the current literature of differential DNA methylation in monocytes from elderly persons vs. young adults across diverse populations. Differentially methylated CpG sites were also noted in gene regions important to inflammation and innate immune responses. Monocytes from Kenyan young adults vs. children displayed increased production of IL-8, IL-10, and IL-12p70 in response to TLR4 and TLR2/1 stimulation as well as distinct inflammatory gene expression profiles. Conclusions These findings complement previous reports of age-related methylation changes in isolated monocytes and provide novel insights into the role of age-associated changes in innate immune functions.

scholarly journals Age-related Differences in Monocyte DNA Methylation and Immune Function in Healthy Kenyan Adults and Children

2020 ◽  
Author(s):  
Katherine Rose Dobbs ◽  
Paula Embury ◽  
Emmily Koech ◽  
Sidney Ogolla ◽  
Stephen Munga ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Young Adults ◽  
Innate Immune ◽  
European Ancestry ◽  
Inflammatory Gene Expression ◽  
Inflammatory Gene ◽  
Cpg Sites ◽  
Age Related ◽  
Adults And Children

Abstract Background: Age-related changes in adaptive and innate immune cells have been associated with a decline in effective immunity and chronic, low-grade inflammation. Epigenetic, transcriptional, and functional changes in monocytes occur with aging, though most studies to date have focused on differences between young adults and the elderly in populations with European ancestry; few data exist regarding changes that occur in circulating monocytes during the first few decades of life or in African populations. We analyzed DNA methylation profiles, cytokine production, and inflammatory gene expression profi 24 les in monocytes from young adults and children from western Kenya.Results: We identified several hypo- and hyper-methylated CpG sites in monocytes from Kenyan young adults vs. children that replicated findings in the current literature of differential DNA methylation in monocytes from elderly persons vs. young adults across diverse populations. Differentially methylated CpG sites were also noted in gene regions important to inflammation and innate immune responses. Monocytes from Kenyan young adults vs. children displayed increased production of IL-8, IL-10, and IL-12p70 in response to TLR4 and TLR2/1 stimulation as well as distinct inflammatory gene expression profiles.Conclusions: These findings complement previous reports of age-related methylation changes in isolated monocytes and provide novel insights into the role of age-associated changes in innate immune functions.

scholarly journals Integrative Analysis of DNA Methylation and Gene Expression Profiles Identifies Colorectal Cancer-Related Diagnostic Biomarkers

2021 ◽  
Vol 27 ◽  
Author(s):  
Mingyue Xu ◽  
Lijun Yuan ◽  
Yan Wang ◽  
Shuo Chen ◽  
Lin Zhang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Dna Methylation ◽  
Logistic Regression Model ◽  
Cpg Island ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Training Set ◽  
Diagnostic Biomarkers ◽  
Cpg Sites

Background: Colorectal cancer (CRC) is a common human malignancy worldwide. The prognosis of patients is largely frustrated by delayed diagnosis or misdiagnosis. DNA methylation alterations have been previously proved to be involved in CRC carcinogenesis.Methods: In this study, we proposed to identify CRC-related diagnostic biomarkers by analyzing DNA methylation and gene expression profiles. TCGA-COAD datasets downloaded from the Cancer Genome Atlas (TCGA) were used as the training set to screen differential expression genes (DEGs) and methylation CpG sites (dmCpGs) in CRC samples. A logistic regression model was constructed based on hyper-methylated CpG sites which were located in downregulated genes for CRC diagnosis. Another two independent datasets from the Gene Expression Omnibus (GEO) were used as a testing set to evaluate the performance of the model in CRC diagnosis.Results: We found that CpG island methylator phenotype (CIMP) was a potential signature of poor prognosis by dividing CRC samples into CIMP and noCIMP groups based on a set of CpG sites with methylation standard deviation (sd) > 0.2 among CRC samples and low methylation levels (mean β < 0.05) in adjacent samples. Hyper-methylated CpGs tended to be more closed to CpG island (CGI) and transcription start site (TSS) relative to hypo-methylated CpGs (p-value < 0.05, Fisher exact test). A logistic regression model was finally constructed based on two hyper-methylated CpGs, which had an area under receiver operating characteristic curve of 0.98 in the training set, and 0.85 and 0.95 in the two independent testing sets.Conclusions: In conclusion, our study identified promising DNA methylation biomarkers for CRC diagnosis.

scholarly journals Identifying Methylation-Driven Immune-related Molecular Subtypes Predicts the Prognosis of Hepatocellular Carcinoma

2021 ◽  
Author(s):  
Qian Yan ◽  
Baoqian Ye ◽  
Boqing Wang ◽  
Wenjiang Zheng ◽  
Xiongwen Wang
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Molecular Subtypes ◽  
Molecular Subtype ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
The Cancer Genome Atlas ◽  
Cpg Sites ◽  
Prognosis Model ◽  
Immune Related Genes

Abstract The purpose of this study is to analyze the DNA methylation and gene expression profiles of immune-related CpG sites to identify the molecular subtypes and CpG sites related to the prognosis of HCC. In this study, the DNA methylation and gene expression datasets were downloaded from The Cancer Genome Atlas database, together with immune-related genes downloaded from the immunology database and analysis portal database to explore the prognostic molecular subtypes of HCC. By performing consistent clustering analysis on 830 immune-related CpG sites, we identified seven subgroups with significant differences in overall survival. Finally, 16 classifiers of immune-related CpG sites were constructed and used in the testing set to verify the prognosis of DNA methylation subgroups, and the results were consistent with the training set. Using the TIMER database, we analyzed 16 immune-related CpG sites expression with the abundance of six types of immune infiltrating cells and found that most are positively correlated with the level of infiltration of multiple immune cells in HCC. This study screened potential immune-related prognostic methylation sites and established a new prognosis model of HCC based on DNA methylation molecular subtype, which may help in the early diagnosis of HCC and developing more effective personalized treatments.

Abstract P098: An Epigenome-wide Study of Obesity in African American Youth and Young Adults: Novel Findings, Replication in Neutrophils and Relationship With Gene Expression

Circulation ◽  
2017 ◽  
Vol 135 (suppl_1) ◽  
Author(s):  
Xiaoling Wang ◽  
Yue Pan ◽  
Haidong Zhu ◽  
Guang Hao ◽  
Xin Wang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Older Adults ◽  
Dna Methylation ◽  
Young Adults ◽  
Methylation Data ◽  
Middle Aged ◽  
Cpg Sites ◽  
Genome Wide ◽  
Obesity Status ◽  
Youth And Young Adults

Background: Several large-scale epigenome wide association studies on obesity-related DNA methylation changes have been published and in total identified 46 CpG sites. These studies were conducted in middle-aged and older adults of Caucasians and African Americans (AAs) using leukocytes. To what extend these signals are independent of cell compositions as well as to what extend they may influence gene expression have not been systematically investigated. Furthermore, the high prevalence of obesity comorbidities in middle-aged or older population may hide or bias obesity itself related DNA methylation changes. Methods: In this study of healthy AA youth and young adults, genome wide DNA methylation data from leukocytes were obtained from three independent studies: EpiGO study (96 obese cases vs. 92 lean controls, aged 14-21, 50% females, test of interest is obesity status), LACHY study (284 participants from general population, aged 14-18, 50% females, test of interest is BMI), and Georgia Stress and Heart study (298 participants from general population, aged 18-38, 52% females, test of interest is BMI) using the Infinium HumanMethylation450 BeadChip. Genome wide DNA methylation data from purified neutrophils as well as genome wide gene expression data from leukocytes using Illumina HT12 V4 array were also obtained for the EpiGO samples. Results: The meta-analysis on the 3 cohorts identified 76 obesity related CpG sites in leukocytes with p<1х10 -7 . Out of the 46 previously identified CpG sites, 36 can be replicated in this AA youth and young adult sample with same direction and p<0.05. Out of the 107 CpG sites including the 36 replicated ones and the 71 newly identified ones, 71 CpG sites (66%) had their relationship with obesity replicated in purified neutrophils (p<0.05). The analysis on the cis regulation of the 107 CpG sites on gene expression showed that 59 CpG sites had at least one gene within 250kb having expression difference between obese cases and lean controls. Furthermore, out of the 59 CpG sites, 6 showed significantly negative correlations and 1 showed significantly positive correlation with the differentially expressed genes. These CpG sites located in SOCS3, CISH, ABCG1, PIM3 and PTGDS genes. Conclusion: In this study of AA youth and young adults, we identified novel CpG sites associated with obesity and replicated majority of the CpG sites previously identified in middle-aged and older adults. For the first time, we showed that majority of the obesity related CpG sites identified from leukocytes are not driven by cell compositions and provided the direct link between DNA methylation-gene expression-obesity status for 7 CpG sites in 5 genes.

scholarly journals Identification of Prognostic Markers in Cholangiocarcinoma Using Altered DNA Methylation and Gene Expression Profiles

2020 ◽  
Vol 11 ◽  
Author(s):  
Nitish Kumar Mishra ◽  
Meng Niu ◽  
Siddesh Southekal ◽  
Prachi Bajpai ◽  
Amr Elkholy ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Prognostic Markers ◽  
Expression Profiles ◽  
Gene Expression Profiles

scholarly journals Hemophilia A Inhibitor Subjects Show Unique PBMC Gene Expression Profiles That Include Up-Regulated Innate Immune Modulators

2020 ◽  
Vol 11 ◽  
Author(s):  
Ahmad Faisal Karim ◽  
Anthony R. Soltis ◽  
Gauthaman Sukumar ◽  
Christoph Königs ◽  
Nadia P. Ewing ◽  
...  
Keyword(s):  
Gene Expression ◽  
Hemophilia A ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Innate Immune ◽  
Immune Modulators

scholarly journals Profiles of Local and Systemic Inflammation in the Outcome of Treatment of Human Cutaneous Leishmaniasis Caused by Leishmania (Viannia)

2019 ◽  
Vol 88 (3) ◽  
Author(s):  
Adriana Navas ◽  
Olga Fernández ◽  
Carolina Gallego-Marín ◽  
María del Mar Castro ◽  
Mariana Rosales-Chilama ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune Responses ◽  
Treatment Failure ◽  
Cutaneous Leishmaniasis ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Neutrophil Activation ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Biopsy Specimens

ABSTRACT The immune mechanisms that contribute to the efficacy of treatment of cutaneous leishmaniasis (CL) are not fully understood. The aim of this study was to define immune correlates of the outcome of treatment of CL caused by Leishmania (Viannia) species during standard of care treatment with pentavalent antimonials. We conducted a comparative expression profiling of immune response genes in peripheral blood mononuclear cells (PBMCs) and lesion biopsy specimens obtained from CL patients before and at the end of treatment (EoT) with meglumine antimoniate. The ex vivo response of PBMCs to L. (V.) panamensis partially reflected that of lesion microenvironments. Significant downregulation of gene expression profiles consistent with local innate immune responses (monocyte and neutrophil activation and chemoattractant molecules) was observed at EoT in biopsy specimens of patients who cured (n = 8), compared to those from patients with treatment failure (n = 8). Among differentially expressed genes, pretreatment expression of CCL2 was significantly predictive of the therapeutic response (receiver operating characteristic [ROC] curve, area under the curve [AUC] = 0.82, P = 0.02). Polymorphisms in regulatory regions of the CCL2 promoter were analyzed in a pilot cohort of DNA samples from CL patients (cures, n = 20, and treatment failure, n = 20), showing putative association of polymorphisms rs13900(C/T) and rs2857656(G/C) with treatment outcome. Our data indicate that dampening gene expression profiles of monocyte and neutrophil activation characterize clinical cure after treatment of CL, supporting participation of parasite-sustained inflammation or deregulated innate immune responses in treatment failure.

Age-related changes in the transcriptional profile of mouse RPE/choroid

2003 ◽  
Vol 15 (3) ◽  
pp. 258-262 ◽  
Author(s):  
Hisashi Ida ◽  
Sharon A. Boylan ◽  
Andrea L. Weigel ◽  
Leonard M. Hjelmeland
Keyword(s):  
Gene Expression ◽  
Expression Profiles ◽  
Cdna Probe ◽  
Gene Expression Profiles ◽  
Age Related Macular Degeneration ◽  
Pcr Analysis ◽  
Rt Pcr ◽  
Mouse Cdna ◽  
Age Related ◽  
Age Related Changes

To evaluate the age-related changes in gene expression occurring in the complex of retinal pigmented epithelium, Bruch’s membrane, and choroid (RPE/choroid), we examined the gene expression profiles of young adult (2 mo) and old (24 mo) male C57BL/6 mice. cDNA probe sets from individual animals were synthesized using total RNA isolated from the RPE/choroid of each animal. Probes were amplified using the Clontech SMART system, radioactively labeled, and hybridized to two different Clontech Atlas mouse cDNA arrays. From each age group, three independent triplicates were hybridized to the arrays. Statistical analyses were performed using the Significance Analysis of Microarrays program (SAM version 1.13; Stanford University). Selected array results were confirmed by semi-quantitative RT-PCR analysis. Of 2,340 genes represented on the arrays, ∼60% were expressed in young and/or old mouse RPE/choroid. A moderate fraction (12%) of all expressed genes exhibited a statistically significant change in expression with age. Of these 150 genes, all but two, HMG14 and carboxypeptidase E, were upregulated with age. Many of these upregulated genes can be grouped into several broad functional categories: immune response, proteases and protease inhibitors, stress response, and neovascularization. RT-PCR results from six of six genes examined confirmed the differential change in expression with age of these genes. Our study provides likely candidate genes to further study their role in the development of age-related macular degeneration and other aging diseases affecting the RPE/choroid.

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