scholarly journals POS0415 BLOOD-DERIVED DNA METHYLATION EPI-SIGNATURES ASSOCIATED WITH ANKYLOSING SPONDYLITIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 437.3-437
Author(s):  
M. Xiao ◽  
J. Gu
Keyword(s):  
Dna Methylation ◽  
Ankylosing Spondylitis ◽  
Mononuclear Cells ◽  
Cell Receptor ◽  
Sample Collection ◽  
Peripheral Blood Mononuclear ◽  
Staff Members ◽  
Expression Of Genes ◽  
Genome Wide ◽  
Receptor Signaling Pathway

Background:Most (~90%) of the ankylosing spondylitis (AS) susceptibility loci are undefined and located in non-coding regions. Epigenetic changes may alter the expression of genes involved in AS and explain part of the missing heritability. 1Objectives:To identify novel DNA methylation sites significant for AS and comprehensively understand the underlying pathological mechanism.Methods:Genome-wide DNA methylation of blood samples from 30 AS patients and 15 health controls was measured on the Infinium® MethylationEPIC BeadChip microarray. Methylome data were analyzed with ChAMP package in R.Results:The epigenome-wide association analysis identified 4,794 differentially methylated positions (DMPs) (FDR <0.05 and delta β >0.05), including 3,294 (68.7%) hypermethylated and 1,500 (31.3%) hypomethylated positions in AS patients (Figure 1A). The identified DMPs allowed clear distinction of most AS cases from controls in the PCA (Figure 1B) and unsupervised hierarchical clustering (Figure 1C). KEGG pathway analysis of AS associated DMPs enriched in T cell receptor signaling pathway, Th1 and Th2 cell differentiation. Besides, a total of 1,048 differentially variable positions (DVPs) were identified, the majority of which (974, 92.9%) were hypervariable in AS, while only 74 DVPs were hypovariable. The increased DNA methylation variability in disease were in line with the previous observation in other diseases, indicating the intrinsic heterogeneity in AS patients, which might be influenced by diverse factors, such as disease activity and treatment.Figure 1.Conclusion:Peripheral blood mononuclear cells from AS patients display aberrant DNA methylome and increased DNA methylation variability. The results enhanced our understanding of the important role of DNA methylation in pathology of AS and offered the possibility of identifying new targets for intervention.References:[1]Whyte JM, Ellis JJ, Brown MA, et al. Best practices in DNA methylation: lessons from inflammatory bowel disease, psoriasis and ankylosing spondylitis. Arthritis Res Ther 2019; 21:133.Acknowledgements:We appreciate all the staff members of the department of rheumatology of the Third Affiliated Hospital of Sun Yat-sen University for assistance and support in the patient’s recruitment and sample collection.Disclosure of Interests:None declared

scholarly journals Genome-Wide DNA Methylation Profiles of Phlegm-Dampness Constitution

2018 ◽  
Vol 45 (5) ◽  
pp. 1999-2008 ◽  
Author(s):  
Haiqiang Yao ◽  
Shanlan Mo ◽  
Ji Wang ◽  
Yingshuai Li ◽  
Chong-Zhi Wang ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Metabolic Disorders ◽  
Mononuclear Cells ◽  
Metabolic Diseases ◽  
Body Type ◽  
Peripheral Blood Mononuclear ◽  
Molecular Features ◽  
Genome Wide ◽  
A Genome ◽  
Differentially Methylated Genes

Background/Aims: Metabolic diseases are leading health concerns in today’s global society. In traditional Chinese medicine (TCM), one body type studied is the phlegm-dampness constitution (PC), which predisposes individuals to complex metabolic disorders. Genomic studies have revealed the potential metabolic disorders and the molecular features of PC. The role of epigenetics in the regulation of PC, however, is unknown. Methods: We analyzed a genome-wide DNA methylation in 12 volunteers using Illumina Infinium Human Methylation450 BeadChip on peripheral blood mononuclear cells (PBMCs). Eight volunteers had PC and 4 had balanced constitutions. Results: Methylation data indicated a genome-scale hyper-methylation pattern in PC. We located 288 differentially methylated probes (DMPs). A total of 256 genes were mapped, and some of these were metabolic-related. SQSTM1, DLGAP2 and DAB1 indicated diabetes mellitus; HOXC4 and SMPD3, obesity; and GRWD1 and ATP10A, insulin resistance. According to Ingenuity Pathway Analysis (IPA), differentially methylated genes were abundant in multiple metabolic pathways. Conclusion: Our results suggest the potential risk for metabolic disorders in individuals with PC. We also explain the clinical characteristics of PC with DNA methylation features.

scholarly journals Genome-Wide DNA Methylation Signatures Predict the Early Asymptomatic Doxorubicin-Induced Cardiotoxicity in Breast Cancer

Cancers ◽  
2021 ◽  
Vol 13 (24) ◽  
pp. 6291
Author(s):  
Michael A. Bauer ◽  
Valentina K. Todorova ◽  
Annjanette Stone ◽  
Weleetka Carter ◽  
Matthew D. Plotkin ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Dna Methylation ◽  
Mononuclear Cells ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Regulation Of Transcription ◽  
Breast Cancer Patients ◽  
Peripheral Blood Mononuclear ◽  
Ventricular Ejection Fraction ◽  
Genome Wide

Chemotherapy with doxorubicin (DOX) may cause unpredictable cardiotoxicity. This study aimed to determine whether the methylation signature of peripheral blood mononuclear cells (PBMCs) prior to and after the first cycle of DOX-based chemotherapy could predict the risk of cardiotoxicity in breast cancer patients. Cardiotoxicity was defined as a decrease in left ventricular ejection fraction (LVEF) by >10%. DNA methylation of PBMCs from 9 patients with abnormal LVEF and 10 patients with normal LVEF were examined using Infinium HumanMethylation450 BeadChip. We have identified 14,883 differentially methylated CpGs at baseline and 18,718 CpGs after the first cycle of chemotherapy, which significantly correlated with LVEF status. Significant differentially methylated regions (DMRs) were found in the promoter and the gene body of SLFN12, IRF6 and RNF39 in patients with abnormal LVEF. The pathway analysis found enrichment for regulation of transcription, mRNA splicing, pathways in cancer and ErbB2/4 signaling. The preliminary results from this study showed that the DNA methylation profile of PBMCs may predict the risk of DOX-induced cardiotoxicity prior to chemotherapy. Further studies with larger cohorts of patients are needed to confirm these findings.

scholarly journals Epigenome wide association study of response to methotrexate in early rheumatoid arthritis patients

PLoS ONE ◽  
2021 ◽  
Vol 16 (3) ◽  
pp. e0247709
Author(s):  
Helen R. Gosselt ◽  
Costanza L. Vallerga ◽  
Pooja R. Mandaviya ◽  
Erik Lubberts ◽  
Johanna M. W. Hazes ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Dna Methylation ◽  
Combination Therapy ◽  
Early Rheumatoid Arthritis ◽  
Mononuclear Cells ◽  
Therapy Response ◽  
Peripheral Blood Mononuclear ◽  
Genome Wide ◽  
Blood Mononuclear Cells ◽  
Meta Analyses

Aim To identify differentially methylated positions (DMPs) and regions (DMRs) that predict response to Methotrexate (MTX) in early rheumatoid arthritis (RA) patients. Materials and methods DNA from baseline peripheral blood mononuclear cells was extracted from 72 RA patients. DNA methylation, quantified using the Infinium MethylationEPIC, was assessed in relation to response to MTX (combination) therapy over the first 3 months. Results Baseline DMPs associated with response were identified; including hits previously described in RA. Additionally, 1309 DMR regions were observed. However, none of these findings were genome-wide significant. Likewise, no specific pathways were related to response, nor could we replicate associations with previously identified DMPs. Conclusion No baseline genome-wide significant differences were identified as biomarker for MTX (combination) therapy response; hence meta-analyses are required.

Distinctive patterns of age-dependent hypomethylation in interspersed repetitive sequences

2010 ◽  
Vol 41 (2) ◽  
pp. 194-200 ◽  
Author(s):  
Pornrutsami Jintaridth ◽  
Apiwat Mutirangura
Keyword(s):  
Mononuclear Cells ◽  
Repetitive Sequences ◽  
Endogenous Retrovirus ◽  
Human Endogenous Retrovirus ◽  
Cellular Functions ◽  
Peripheral Blood Mononuclear ◽  
Global Methylation ◽  
Short Interspersed Elements ◽  
Genome Wide ◽  
Age Dependent

Interspersed repetitive sequences (IRSs) are a major contributor to genome size and may contribute to cellular functions. IRSs are subdivided according to size and functionally related structures into short interspersed elements, long interspersed elements (LINEs), DNA transposons, and LTR-retrotransposons. Many IRSs may produce RNA and regulate genes by a variety of mechanisms. The majority of DNA methylation occurs in IRSs and is believed to suppress IRS activities. Global hypomethylation, or the loss of genome-wide methylation, is a common epigenetic event not only in senescent cells but also in cancer cells. Loss of LINE-1 methylation has been characterized in many cancers. Here, we evaluated the methylation levels of peripheral blood mononuclear cells of LINE-1, Alu, and human endogenous retrovirus K (HERV-K) in 177 samples obtained from volunteers between 20 and 88 yr of age. Age was negatively associated with methylation levels of Alu (r = −0.452, P < 10−3) and HERV-K (r = −0.326, P < 10−3) but not LINE-1 (r = 0.145, P = 0.055). Loss of methylation of Alu occurred during ages 34–68 yr, and loss of methylation of HERV-K occurred during ages 40–63 yr and again during ages 64–83 yr. Interestingly, methylation of Alu and LINE-1 are directly associated, particularly at ages 49 yr and older (r = 0.49, P < 10−3). Therefore, only some types of IRSs lose methylation at certain ages. Moreover, Alu and HERV-K become hypomethylated differently. Finally, there may be several mechanisms of global methylation. However, not all of these mechanisms are age-dependent. This finding may lead to a better understanding of not only the biological causes and consequences of genome-wide hypomethylation but also the role of IRSs in the aging process.

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