Clinical Epigenetics最新文献

{"title":"DNA methylation models of protein abundance across the lifecourse.","authors":"Scott Waterfield, Paul Yousefi, Matt Suderman","doi":"10.1186/s13148-024-01802-y","DOIUrl":"https://doi.org/10.1186/s13148-024-01802-y","url":null,"abstract":"<p><strong>Background: </strong>Multiple studies have shown that DNA methylation (DNAm) models of protein abundance can be informative about exposure, phenotype and disease risk. Here we investigate and provide descriptive details of the capacity of DNAm to capture non-genetic variation in protein abundance across the lifecourse.</p><p><strong>Methods: </strong>We evaluated the performance of 14 previously published DNAm models of protein abundance (episcores) in peripheral blood from a large adult population using the Avon Longitudinal Study of Parents and Children (ALSPAC) at ages 7-24 and their mothers antenatally and in middle age (N range = 145-1464). New age-specific episcores were trained in ALSPAC and evaluated at different ages. In all instances, episcore-protein associations were evaluated with and without adjustment for genetics. The association between longitudinal protein stability and longitudinal episcore projection was also evaluated, as was sex-specificity of episcores derived solely in female participants.</p><p><strong>Findings: </strong>Of the 14 Gadd episcores, 10 generated estimates associated with abundance in middle age, 9 at age 24, and none at age 9. Eight of these episcores explained variation beyond genotype in adulthood (6 at age 24; 7 at midlife). At age 9, the abundances of 22 proteins could be modelled by DNAm, 7 beyond genotype of which one trained model generated informative estimates at ages 24 and in middle age. At age 24, 31 proteins could be modelled by DNAm, 19 beyond genotype, of which 5 trained models generated informative estimates at age 9 and 8 in middle age. In middle age, 23 proteins could be modelled, 13 beyond genotype, of which 3 were informative at age 9 and 7 at age 24.</p><p><strong>Interpretation: </strong>We observed that episcores performed better at older ages than in children with several episcores capturing non-genetic variation at all ages.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"16 1","pages":"189"},"PeriodicalIF":4.8,"publicationDate":"2024-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142871554","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-cell transcriptomics reveal the prognostic roles of epithelial and T cells and DNA methylation-based prognostic models in pancreatic cancer.","authors":"Jing Du, Yaqian Zhao, Jie Dong, Peng Li, Yan Hu, Hailang Fan, Feifan Zhang, Lanlan Sun, Dake Zhang, Yuhua Zhang","doi":"10.1186/s13148-024-01800-0","DOIUrl":"https://doi.org/10.1186/s13148-024-01800-0","url":null,"abstract":"<p><strong>Background: </strong>Pancreatic adenocarcinoma (PDAC) exhibits a complex microenvironment with diverse cell populations influencing patient prognosis. Single-cell RNA sequencing (scRNA-seq) was used to identify prognosis-related cell types, and DNA methylation (DNAm)-based models were developed to predict outcomes based on their cellular characteristics.</p><p><strong>Methods: </strong>We integrated scRNA-seq, bulk data, and clinical information to identify key cell populations associated with prognosis. The TCGA dataset was used for validation, and cell composition was inferred from DNAm data. Prognostic models were constructed based on cell-type-specific DNAm markers, and genomic features were compared across risk groups. Nomograms were created to assess treatment responses in different risk levels.</p><p><strong>Results: </strong>Epithelial and T cells were major prognostic factors. Genomic analysis showed that epithelial cells in PDAC followed a malignant trajectory. DNAm data from TCGA confirmed the association of higher epithelial and T cell proportions with worse prognosis. Prognostic models based on DNAm markers of these cells effectively predicted patient survival, especially 5-year overall survival (AUC = 0.834). High-risk group with epithelial cell model showed altered pathways (tight junctions, NOTCH, and P53 signaling), while high-risk group with T cell model had changes in glycolysis, hypoxia, and NOTCH signaling, with more KRAS or TP53 mutations. Low-risk groups in the T cell model displayed stronger antitumor immune responses. Treatment predictions and nomograms were developed for clinical use.</p><p><strong>Conclusions: </strong>scRNA-seq and DNAm data integration enabled the creation of predictive models based on epithelial and T cell-specific methylation patterns, offering robust prognosis prediction for PDAC patients.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"16 1","pages":"188"},"PeriodicalIF":4.8,"publicationDate":"2024-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142871560","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Maximizing insights from longitudinal epigenetic age data: simulations, applications, and practical guidance.","authors":"Anna Großbach, Matthew J Suderman, Anke Hüls, Alexandre A Lussier, Andrew D A C Smith, Esther Walton, Erin C Dunn, Andrew J Simpkin","doi":"10.1186/s13148-024-01784-x","DOIUrl":"https://doi.org/10.1186/s13148-024-01784-x","url":null,"abstract":"<p><strong>Background: </strong>Epigenetic age (EA) is an age estimate, developed using DNA methylation (DNAm) states of selected CpG sites across the genome. Although EA and chronological age are highly correlated, EA may not increase uniformly with time. Departures, known as epigenetic age acceleration (EAA), are common and have been linked to various traits and future disease risk. Limited by available data, most studies investigating these relationships have been cross-sectional, using a single EA measurement. However, the recent growth in longitudinal DNAm studies has led to analyses of associations with EA over time. These studies differ in (1) their choice of model; (2) the primary outcome (EA vs. EAA); and (3) in their use of chronological age or age-independent time variables to account for the temporal dynamic. We evaluated the robustness of each approach using simulations and tested our results in two real-world examples, using biological sex and birthweight as predictors of longitudinal EA.</p><p><strong>Results: </strong>Our simulations showed most accurate effect sizes in a linear mixed model or generalized estimating equation, using chronological age as the time variable. The use of EA versus EAA as an outcome did not strongly impact estimates. Applying the optimal model in real-world data uncovered advanced GrimAge in individuals assigned male at birth that decelerates over time.</p><p><strong>Conclusion: </strong>Our results can serve as a guide for forthcoming longitudinal EA studies, aiding in methodological decisions that may determine whether an association is accurately estimated, overestimated, or potentially overlooked.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"16 1","pages":"187"},"PeriodicalIF":4.8,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142871555","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Exploring the therapeutic potential of Sirt6-enriched adipose stem cell-derived exosomes in myocardial ischemia-reperfusion injury: unfolding new epigenetic frontiers.","authors":"Kun Liu, Hecheng Wang, Yiou Wang, Xiaoxu Zhang, Ruihu Wang, Zhaoxuan Zhang, Jian Wang, Xinran Lu, Xiaoyu Wu, Yanshuo Han","doi":"10.1186/s13148-024-01796-7","DOIUrl":"https://doi.org/10.1186/s13148-024-01796-7","url":null,"abstract":"","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"16 1","pages":"186"},"PeriodicalIF":4.8,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142871553","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"BET inhibition revealed varying MYC dependency mechanisms independent of gene alterations in aggressive B-cell lymphomas.","authors":"Loris Delrieu, Sieme Hamaidia, Emilie Montaut, Andrea Cecilia Garcia-Sandoval, Camille Teste, Patricia Betton-Fraisse, Thierry Bonnefoix, Sylvain Carras, Rémy Gressin, Christine Lefebvre, Jérôme Govin, Anouk Emadali","doi":"10.1186/s13148-024-01788-7","DOIUrl":"https://doi.org/10.1186/s13148-024-01788-7","url":null,"abstract":"<p><strong>Background: </strong>MYC-driven lymphomas are a subset of B-cell lymphomas characterized by genetic alterations that dysregulate the expression of the MYC oncogene. When overexpressed, typically through chromosomal translocations, amplifications, or other mechanisms, MYC can drive uncontrolled cell growth and contribute to cancer development. MYC-driven lymphomas are described as aggressive entities which require intensive treatment approaches and can be associated with poor prognosis. In the absence of direct MYC-targeting therapy, epigenetic drugs called BET inhibitors (BETi) were shown to reduce MYC levels by disrupting BRD4-dependent transcription associated with the expression of MYC, as well as other oncogenes. Here, we used BETi as molecular tools to better understand oncogenic dependencies in a panel of cell line models of MYC-driven B-cell lymphoma selected to represent their genetic heterogeneity.</p><p><strong>Results: </strong>We first showed that, in these models, MYC expression level does not strictly correlate to the presence of gene alterations. Our data also demonstrated that BETi induces similar growth arrest in all lymphoma cell lines independently of MYC mutational status or expression level. In contrast, BETi-induced cell death was only observed in two cell lines presenting the highest level of MYC protein. This suggests that some MYC-driven lymphoma could present a stronger dependency on MYC for their survival which cannot be predicted on the sole basis on their genetics. This hypothesis was confirmed by gene invalidation experiments, which showed that MYC loss recapitulates the effect of BETi treatment on both cell proliferation and survival, confirming MYC oncogene dependency in models sensitive to BETi cytotoxicity. In contrast, the growth arrest observed in cell lines resistant to BETi-induced apoptosis is not mediated through MYC, but rather through alternative pro-proliferative or oncogenic pathways. Gene expression profiling revealed the basal activation of a specific non-canonical WNT/Hippo pathway in cell death-resistant cell lines that could be targeted in combination therapy to restore BETi cytotoxicity.</p><p><strong>Conclusion: </strong>This work brings new insights into the complexity of MYC-dependencies and unravels a novel targetable oncogenic pathway in aggressive B-cell lymphomas.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"16 1","pages":"185"},"PeriodicalIF":4.8,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142863234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Distinct microbiome dysbiosis and epigenetic anomaly in esophageal adenocarcinoma and its underlying Barrett's esophagus.","authors":"Takuya Shijimaya, Tomomitsu Tahara, Jumpei Yamazaki, Sanshiro Kobayashi, Yasushi Matsumoto, Naohiro Nakamura, Yu Takahashi, Takashi Tomiyama, Toshiro Fukui, Tomoyuki Shibata, Makoto Naganuma","doi":"10.1186/s13148-024-01801-z","DOIUrl":"https://doi.org/10.1186/s13148-024-01801-z","url":null,"abstract":"<p><p>Interaction between host genotoxic changes and mucosa-associated microbiome (MAM) dysbiosis may have a role in various digestive cancers. We investigated MAM in Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC) progression sequence and its association with host genotoxic changes. 16S rRNA gene sequencing was performed in three different groups of biopsies from nonneoplastic BE from patients without cancer (N, normal group; n = 47) and with EAC (ADJ, adjacent group; n = 27). Endoscopic biopsies were also obtained from EAC tissues (T, tumor group; n = 22). Results were correlated with TP53 mutation, telomere length and DNA methylation of candidate genes (N33, DPYS, SLC16A12, miR124A3 and miR34bc). Genome-wide DNA methylation examined by reduced representation bisulfite sequencing (RRBS) was available for 32 samples (n = 12 for N, n = 12 for ADJ and n = 22 for T groups). Lower microbial alpha diversity measures were observed in ADJ/T groups relative to N group and associated with higher mean Z score DNA methylation of candidate genes. Specific genera (n = 16) with significant change between ADJ/T groups relative to N group occurred mostly in ADJ group (13/16) and half of them (8/16) were associated with DNA methylation status. Integrated MAM and genome-wide methylation analysis demonstrated that hyper-methylated sites, associated with lower alpha diversity measures dominantly occurred within near the transcription start site, codifying genes were involved in metabolic processes. Our result shows that microbial dysbiosis in EAC mostly occurs in adjacent BE and such dysbiosis was associated with DNA methylation status, offering support for a pathogenic role of interaction between host genotoxic changes and MAM in this tumor type.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"16 1","pages":"184"},"PeriodicalIF":4.8,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142863357","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advancing diagnosis and early risk assessment of preeclampsia through noninvasive cell-free DNA methylation profiling.","authors":"Machteld Baetens, Bram Van Gaever, Stephanie Deblaere, Andries De Koker, Leander Meuris, Nico Callewaert, Sandra Janssens, Kristien Roelens, Ellen Roets, Jo Van Dorpe, Isabelle Dehaene, Björn Menten","doi":"10.1186/s13148-024-01798-5","DOIUrl":"https://doi.org/10.1186/s13148-024-01798-5","url":null,"abstract":"<p><strong>Background: </strong>Aberrant embryo implantation and suboptimal placentation can lead to (severe) complications such as preeclampsia and fetal growth restriction later in pregnancy. Current identification of high-risk pregnancies relies on a combination of risk factors, biomarkers, and ultrasound examinations, a relatively inaccurate approach. Previously, aberrant DNA methylation due to placental hypoxia has been identified as a potential marker of placental insufficiency and, hence, potential (future) pregnancy complications. The goal of the Early Prediction of prEgnancy Complications Testing, or the ExPECT study, is to validate a genome-wide, cell-free DNA (cfDNA) methylation strategy to diagnose preeclampsia accurately. More importantly, the predictive potential of this strategy is also explored to reliably identify high-risk pregnancies early in gestation. Furthermore, a longitudinal study was conducted, including sequential blood samples from pregnant individuals experiencing both uneventful and complicated gestations, to assess the methylation dynamics of cfDNA throughout these pregnancies. A significant strength of this study is its enzymatic digest, which enriches CpG-rich regions across the genome without the need for proprietary reagents or prior selection of regions of interest. This makes it useful for the cost-effective discovery of novel markers.</p><p><strong>Results: </strong>Investigation of methylation patterns throughout pregnancy showed different methylation trends between unaffected and affected pregnancies. We detected differentially methylated regions (DMRs) in pregnancies complicated with preeclampsia as early as 12 weeks of gestation, with distinct differences in the methylation profile between early and late pregnancy. Two classification models were developed to diagnose and predict preeclampsia, demonstrating promising results on a small set of validation samples.</p><p><strong>Conclusions: </strong>This study offers valuable insights into methylation changes at specific genomic regions throughout pregnancy, revealing critical differences between normal and complicated pregnancies. The power of noninvasive cfDNA methylation profiling was successfully proven, suggesting the potential to integrate this noninvasive approach into routine prenatal care.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"16 1","pages":"182"},"PeriodicalIF":4.8,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142853309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Changes in DNA methylation are associated with systemic lupus erythematosus flare remission and clinical subtypes.","authors":"Mary K Horton, Joanne Nititham, Kimberly E Taylor, Patricia Katz, Chun Jimmie Ye, Jinoos Yazdany, Maria Dall'Era, Charlotte Hurabielle, Lisa F Barcellos, Lindsey A Criswell, Cristina M Lanata","doi":"10.1186/s13148-024-01792-x","DOIUrl":"https://doi.org/10.1186/s13148-024-01792-x","url":null,"abstract":"<p><strong>Background: </strong>Systemic lupus erythematosus (SLE) has numerous symptoms across organs and an unpredictable flare-remittance pattern. This has made it challenging to understand drivers of long-term SLE outcomes. Our objective was to identify whether changes in DNA methylation over time, in an actively flaring SLE cohort, were associated with remission and whether these changes meaningfully subtype SLE patients.</p><p><strong>Methods: </strong>Fifty-nine multi-ethnic SLE patients had clinical visits and DNA methylation profiles at a flare and approximately 3 months later. Methylation was measured using the Illumina EPIC array. We identified sites where methylation change between visits was associated with remission at the follow-up visit using limma package and a time x remission interaction term. Models adjusted for batch, age at diagnosis, time between visits, age at flare, sex, medications, and cell-type proportions. Separately, a paired T-test identified Bonferroni significant methylation sites with ≥ 3% change between visits (n = 546). Methylation changes at these sites were used for unsupervised consensus hierarchical clustering. Associations between clusters and patient features were assessed.</p><p><strong>Results: </strong>Nineteen patients fully remitted at the follow-up visit. For 1,953 CpG sites, methylation changed differently for remitters vs. non-remitters (Bonferroni p < 0.05). Nearly half were within genes regulated by interferon. The largest effect was at cg22873177; on average, remitters had 23% decreased methylation between visits while non-remitters had no change. Three SLE patient clusters were identified using methylation differences agnostic of clinical outcomes. All Cluster 1 subjects (n = 12) experienced complete flare remission, despite similar baseline disease activity scores, medications, and demographics as other clusters. Methylation changes at six CpG sites, including within immune-related CD45 and IFI genes, were particularly distinct for each cluster, suggesting these may be good candidates for stratifying patients in the future.</p><p><strong>Conclusions: </strong>Changes in DNA methylation during active SLE were associated with remission status and identified subgroups of SLE patients with several distinct clinical and biological characteristics. DNA methylation patterns might help inform SLE subtypes, leading to targeted therapies based on relevant underlying biological pathways.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"16 1","pages":"181"},"PeriodicalIF":4.8,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142853310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epigenome-wide mediation analysis of the relationship between psychosocial stress and cardiometabolic risk factors in the Health and Retirement Study (HRS).","authors":"Lauren A Opsasnick, Wei Zhao, Scott M Ratliff, Jiacong Du, Jessica D Faul, Lauren L Schmitz, Xiang Zhou, Belinda L Needham, Jennifer A Smith","doi":"10.1186/s13148-024-01799-4","DOIUrl":"https://doi.org/10.1186/s13148-024-01799-4","url":null,"abstract":"<p><strong>Background: </strong>Exposure to psychosocial stress is linked to a variety of negative health outcomes, including cardiovascular disease and its cardiometabolic risk factors. DNA methylation has been associated with both psychosocial stress and cardiometabolic disease; however, little is known about the mediating role of DNA methylation on the association between stress and cardiometabolic risk. Thus, using the high-dimensional mediation testing method, we conducted an epigenome-wide mediation analysis of the relationship between psychosocial stress and ten cardiometabolic risk factors in a multi-racial/ethnic population of older adults (n = 2668) from the Health and Retirement Study (mean age = 70.4 years).</p><p><strong>Results: </strong>A total of 50, 46, 7, and 12 CpG sites across the epigenome mediated the total effects of stress on body mass index, waist circumference, high-density lipoprotein cholesterol, and C-reactive protein, respectively. When reducing the dimensionality of the CpG mediators to their top 10 uncorrelated principal components (PC), the cumulative effect of the PCs explained between 35.8 and 46.3% of these associations.</p><p><strong>Conclusions: </strong>A subset of the mediating CpG sites were associated with the expression of genes enriched in pathways related to cytokine binding and receptor activity, as well as neuron development. Findings from this study help to elucidate the underlying mechanisms through which DNA methylation partially mediates the relationship between psychosocial stress and cardiometabolic risk factors.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"16 1","pages":"180"},"PeriodicalIF":4.8,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142853312","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epigenetic regulation on left atrial function and disease recurrence after catheter ablation in atrial fibrillation.","authors":"Mi-Ryung Han, Joo Hee Jeong, Yun Gi Kim, Hyun-Ho Yang, Chang-Ok Seo, Yeji Kim, Hyoung Seok Lee, Jaemin Shim, Young-Hoon Kim, Jong-Il Choi","doi":"10.1186/s13148-024-01794-9","DOIUrl":"https://doi.org/10.1186/s13148-024-01794-9","url":null,"abstract":"<p><strong>Background: </strong>Genetic variation and modifiable risk factors play a significant role in the pathogenesis of atrial fibrillation (AF). The influence of epigenetic modification on AF remains to be elucidated. We investigated the role of DNA methylation in the etiology of AF. Epigenetic evaluation was performed in 115 AF patients who underwent radiofrequency catheter ablation in a single institution. We measured methylation at approximately 850,000 bp cytosine-phosphate-guanine (CpG) sites in the 115 samples. The degree of methylation was compared across seven classification criteria: type of AF, late recurrence, impaired left atrium (LA) function, late gadolinium enhancement, LA diameter, LA volume, and flow velocity of the LA appendage.</p><p><strong>Results: </strong>The four most significantly methylated genes were DEFB104B, C3, TANC1, and TMEM9B. The DEFB104B gene (cg20223677 in the transcription start site), which encodes β-defensin 104B, was hypomethylated in three groups: AF patients with late recurrence, impaired LA function, and impaired LAA flow velocity. Enriched functional annotation of the differentially methylated datasets revealed that five out of the seven AF groups in this cohort were associated with genes involved in the cell movement of endothelial cell lines, sprouting angiogenesis by endothelial cell lines, or migration of endothelial cell lines.</p><p><strong>Conclusions: </strong>Epigenetic profiling revealed that epigenetic modification might affect important characteristics of AF. Our results suggest that the pathogenesis of AF might be affected by not only genetic variation or modifiable factors but also by epigenetic modulation.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"16 1","pages":"183"},"PeriodicalIF":4.8,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142853311","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}