Clinical Epigenetics最新文献

{"title":"Aortic disease and cardiomyopathy in patients with a novel DNMT3A gene variant causing Tatton-Brown-Rahman syndrome.","authors":"Dovile Zebrauskiene, Egle Sadauskiene, Justas Dapkunas, Visvaldas Kairys, Joris Balciunas, Aleksandras Konovalovas, Ruta Masiuliene, Gunda Petraityte, Nomeda Valeviciene, Mindaugas Mataciunas, Jurate Barysiene, Violeta Mikstiene, Migle Tomkuviene, Egle Preiksaitiene","doi":"10.1186/s13148-024-01686-y","DOIUrl":"10.1186/s13148-024-01686-y","url":null,"abstract":"<p><p>Tatton-Brown-Rahman syndrome (TBRS) is a rare congenital genetic disorder caused by autosomal dominant pathogenic variants in the DNA methyltransferase DNMT3A gene. Typical TBRS clinical features are overgrowth, intellectual disability, and minor facial anomalies. However, since the syndrome was first described in 2014, a widening spectrum of abnormalities is being described. Cardiovascular abnormalities are less commonly reported but can be a major complication of the syndrome. This article describes a family of three individuals diagnosed with TBRS in adulthood and highlights the variable expression of cardiovascular features. A 34-year-old proband presented with progressive aortic dilatation, mitral valve (MV) regurgitation, left ventricular (LV) dilatation, and ventricular arrhythmias. The affected family members (mother and brother) were diagnosed with MV regurgitation, LV dilatation, and arrhythmias. Exome sequencing and computational protein analysis suggested that the novel familial DNMT3A mutation Ser775Tyr is located in the methyltransferase domain, however, distant from the active site or DNA-binding loops. Nevertheless, this bulky substitution may have a significant effect on DNMT3A protein structure, dynamics, and function. Analysis of peripheral blood cfDNA and transcriptome showed shortened mononucleosome fragments and altered gene expression in a number of genes related to cardiovascular health and of yet undescribed function, including several lncRNAs. This highlights the importance of epigenetic regulation by DNMT3A on cardiovascular system development and function. From the clinical perspective, we suggest that new patients diagnosed with congenital DNMT3A variants and TBRS require close examination and follow-up for aortic dilatation and valvular disease because these conditions can progress rapidly. Moreover, personalized treatments, based on the specific DNMT3A variants and the different pathways of their function loss, can be envisioned in the future.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"16 1","pages":"76"},"PeriodicalIF":4.8,"publicationDate":"2024-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11157947/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141283103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DNA methylation and stroke prognosis: an epigenome-wide association study.","authors":"Joan Jiménez-Balado, Isabel Fernández-Pérez, Cristina Gallego-Fábrega, Uxue Lazcano, Carolina Soriano-Tárraga, Marta Vallverdú-Prats, Marina Mola-Caminal, Lucía Rey-Álvarez, Adrià Macias-Gómez, Antoni Suárez-Pérez, Eva Giralt-Steinhauer, Ana Rodríguez-Campello, Elisa Cuadrado-Godia, Ángel Ois, Manel Esteller, Jaume Roquer, Israel Fernández-Cadenas, Jordi Jiménez-Conde","doi":"10.1186/s13148-024-01690-2","DOIUrl":"10.1186/s13148-024-01690-2","url":null,"abstract":"<p><strong>Background and aims: </strong>Stroke is the leading cause of adult-onset disability. Although clinical factors influence stroke outcome, there is a significant variability among individuals that may be attributed to genetics and epigenetics, including DNA methylation (DNAm). We aimed to study the association between DNAm and stroke prognosis.</p><p><strong>Methods and results: </strong>To that aim, we conducted a two-phase study (discovery-replication and meta-analysis) in Caucasian patients with ischemic stroke from two independent centers (BasicMar [discovery, N = 316] and St. Pau [replication, N = 92]). Functional outcome was assessed using the modified Rankin Scale (mRS) at three months after stroke, being poor outcome defined as mRS > 2. DNAm was determined using the 450K and EPIC BeadChips in whole-blood samples collected within the first 24 h. We searched for differentially methylated positions (DMPs) in 370,344 CpGs, and candidates below p-value < 10^-5 were subsequently tested in the replication cohort. We then meta-analyzed DMP results from both cohorts and used them to identify differentially methylated regions (DMRs). After doing the epigenome-wide association study, we found 29 DMPs at p-value < 10^-5 and one of them was replicated: cg24391982, annotated to thrombospondin-2 (THBS2) gene (p-value_discovery = 1.54·10^-6; p-value_replication = 9.17·10^-4; p-value_{meta-analysis} = 6.39·10^-9). Besides, four DMRs were identified in patients with poor outcome annotated to zinc finger protein 57 homolog (ZFP57), Arachidonate 12-Lipoxygenase 12S Type (ALOX12), ABI Family Member 3 (ABI3) and Allantoicase (ALLC) genes (p-value < 1·10^-9 in all cases).</p><p><strong>Discussion: </strong>Patients with poor outcome showed a DMP at THBS2 and four DMRs annotated to ZFP57, ALOX12, ABI3 and ALLC genes. This suggests an association between stroke outcome and DNAm, which may help identify new stroke recovery mechanisms.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"16 1","pages":"75"},"PeriodicalIF":5.7,"publicationDate":"2024-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11155152/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141283104","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Consistent cord blood DNA methylation signatures of gestational age between South Asian and white European cohorts.","authors":"Wei Q Deng, Marie Pigeyre, Sandi M Azab, Samantha L Wilson, Natalie Campbell, Nathan Cawte, Katherine M Morrison, Stephanie A Atkinson, Padmaja Subbarao, Stuart E Turvey, Theo J Moraes, Piush Mandhane, Meghan B Azad, Elinor Simons, Guillaume Pare, Sonia S Anand","doi":"10.1186/s13148-024-01684-0","DOIUrl":"10.1186/s13148-024-01684-0","url":null,"abstract":"<p><strong>Background: </strong>Epigenetic modifications, particularly DNA methylation (DNAm) in cord blood, are an important biological marker of how external exposures during gestation can influence the in-utero environment and subsequent offspring development. Despite the recognized importance of DNAm during gestation, comparative studies to determine the consistency of these epigenetic signals across different ethnic groups are largely absent. To address this gap, we first performed epigenome-wide association studies (EWAS) of gestational age (GA) using newborn cord blood DNAm comparatively in a white European (n = 342) and a South Asian (n = 490) birth cohort living in Canada. Then, we capitalized on established cord blood epigenetic GA clocks to examine the associations between maternal exposures, offspring characteristics and epigenetic GA, as well as GA acceleration, defined as the residual difference between epigenetic and chronological GA at birth.</p><p><strong>Results: </strong>Individual EWASs confirmed 1,211 and 1,543 differentially methylated CpGs previously reported to be associated with GA, in white European and South Asian cohorts, respectively, with a similar distribution of effects. We confirmed that Bohlin's cord blood GA clock was robustly correlated with GA in white Europeans (r = 0.71; p = 6.0 × 10^-54) and South Asians (r = 0.66; p = 6.9 × 10^-64). In both cohorts, Bohlin's clock was positively associated with newborn weight and length and negatively associated with parity, newborn female sex, and gestational diabetes. Exclusive to South Asians, the GA clock was positively associated with the newborn ponderal index, while pre-pregnancy weight and gestational weight gain were strongly predictive of increased epigenetic GA in white Europeans. Important predictors of GA acceleration included gestational diabetes mellitus, newborn sex, and parity in both cohorts.</p><p><strong>Conclusions: </strong>These results demonstrate the consistent DNAm signatures of GA and the utility of Bohlin's GA clock across the two populations. Although the overall pattern of DNAm is similar, its connections with the mother's environment and the baby's anthropometrics can differ between the two groups. Further research is needed to understand these unique relationships.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"16 1","pages":"74"},"PeriodicalIF":5.7,"publicationDate":"2024-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11155053/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141261030","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pathogenic sequence variant and microdeletion affecting HMGA2 in Silver-Russell syndrome: case reports and literature review.","authors":"Kaori Yamoto, Hirotomo Saitsu, Yumiko Ohkubo, Masayo Kagami, Tsutomu Ogata","doi":"10.1186/s13148-024-01688-w","DOIUrl":"10.1186/s13148-024-01688-w","url":null,"abstract":"<p><p>Silver-Russell syndrome (SRS) is a representative imprinting disorder characterized by pre- and postnatal growth failure. We encountered two Japanese SRS cases with a de novo pathogenic frameshift variant of HMGA2 (NM_003483.6:c.138_141delinsCT, p.(Lys46Asnfs*16)) and a de novo ~ 3.4 Mb microdeletion at 12q14.2-q15 involving HMGA2, respectively. Furthermore, we compared clinical features in previously reported patients with various genetic conditions leading to compromised IGF2 expression, i.e., HMGA2 aberrations, PLAG1 aberrations, IGF2 aberrations, and H19/IGF2:IG-DMR epimutations (hypomethylations). The results provide further support for HMGA2 being involved in the development of SRS and imply some characteristic features in patients with HMGA2 aberrations.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"16 1","pages":"73"},"PeriodicalIF":4.8,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11155105/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141261044","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lactylation: the novel histone modification influence on gene expression, protein function, and disease.","authors":"Yue Hu, Zhenglin He, Zongjun Li, Yihan Wang, Nan Wu, Hongyan Sun, Zilong Zhou, Qianying Hu, Xianling Cong","doi":"10.1186/s13148-024-01682-2","DOIUrl":"10.1186/s13148-024-01682-2","url":null,"abstract":"<p><p>Lactic acid, traditionally considered as a metabolic waste product arising from glycolysis, has undergone a resurgence in scientific interest since the discovery of the Warburg effect in tumor cells. Numerous studies have proved that lactic acid could promote angiogenesis and impair the function of immune cells within tumor microenvironments. Nevertheless, the precise molecular mechanisms governing these biological functions remain inadequately understood. Recently, lactic acid has been found to induce a posttranslational modification, lactylation, that may offer insight into lactic acid's non-metabolic functions. Notably, the posttranslational modification of proteins by lactylation has emerged as a crucial mechanism by which lactate regulates cellular processes. This article provides an overview of the discovery of lactate acidification, outlines the potential \"writers\" and \"erasers\" responsible for protein lactylation, presents an overview of protein lactylation patterns across different organisms, and discusses the diverse physiological roles of lactylation. Besides, the article highlights the latest research progress concerning the regulatory functions of protein lactylation in pathological processes and underscores its scientific significance for future investigations.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"16 1","pages":"72"},"PeriodicalIF":5.7,"publicationDate":"2024-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11138093/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141174191","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"No association between peripheral serotonin-gene-related DNA methylation and brain serotonin neurotransmission in the healthy and depressed state.","authors":"S E P Bruzzone, B Ozenne, P M Fisher, G Ortega, P S Jensen, V H Dam, C Svarer, G M Knudsen, K P Lesch, V G Frokjaer","doi":"10.1186/s13148-024-01678-y","DOIUrl":"10.1186/s13148-024-01678-y","url":null,"abstract":"<p><strong>Background: </strong>Methylation of serotonin-related genes has been proposed as a plausible gene-by-environment link which may mediate environmental stress, depressive and anxiety symptoms. DNA methylation is often measured in blood cells, but little is known about the association between this peripheral epigenetic modification and brain serotonergic architecture. Here, we evaluated the association between whole-blood-derived methylation of four CpG sites in the serotonin transporter (SLC6A4) and six CpG sites of the tryptophan hydroxylase 2 (TPH2) gene and in-vivo brain levels of serotonin transporter (5-HTT) and serotonin 4 receptor (5-HT₄) in a cohort of healthy individuals (N = 254) and, for 5-HT_4, in a cohort of unmedicated patients with depression (N = 90). To do so, we quantified SLC6A4/TPH2 methylation using bisulfite pyrosequencing and estimated brain 5-HT₄ and 5-HTT levels using positron emission tomography. In addition, we explored the association between SLC6A4 and TPH2 methylation and measures of early life and recent stress, depressive and anxiety symptoms on 297 healthy individuals.</p><p><strong>Results: </strong>We found no statistically significant association between peripheral DNA methylation and brain markers of serotonergic neurotransmission in patients with depression or in healthy individuals. In addition, although SLC6A4 CpG2 (chr17:30,236,083) methylation was marginally associated with the parental bonding inventory overprotection score in the healthy cohort, statistical significance did not remain after accounting for blood cell heterogeneity.</p><p><strong>Conclusions: </strong>We suggest that findings on peripheral DNA methylation in the context of brain serotonin-related features should be interpreted with caution. More studies are needed to rule out a role of SLC6A4 and TPH2 methylation as biomarkers for environmental stress, depressive or anxiety symptoms.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"16 1","pages":"71"},"PeriodicalIF":5.7,"publicationDate":"2024-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11131311/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141157411","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Longitudinal analysis of epigenome-wide DNA methylation reveals novel loci associated with BMI change in East Asians.","authors":"Wenran Li, Mingfeng Xia, Hailuan Zeng, Huandong Lin, Andrew E Teschendorff, Xin Gao, Sijia Wang","doi":"10.1186/s13148-024-01679-x","DOIUrl":"10.1186/s13148-024-01679-x","url":null,"abstract":"<p><strong>Background: </strong>Obesity is a global public health concern linked to chronic diseases such as cardiovascular disease and type 2 diabetes (T2D). Emerging evidence suggests that epigenetic modifications, particularly DNA methylation, may contribute to obesity. However, the molecular mechanism underlying the longitudinal change of BMI has not been well-explored, especially in East Asian populations.</p><p><strong>Methods: </strong>This study performed a longitudinal epigenome-wide association analysis of DNA methylation to uncover novel loci associated with BMI change in 533 individuals across two Chinese cohorts with repeated DNA methylation and BMI measurements over four years.</p><p><strong>Results: </strong>We identified three novel CpG sites (cg14671384, cg25540824, and cg10848724) significantly associated with BMI change. Two of the identified CpG sites were located in regions previously associated with body shape and basal metabolic rate. Annotation of the top 20 BMI change-associated CpGs revealed strong connections to obesity and T2D. Notably, these CpGs exhibited active regulatory roles and located in genes with high expression in the liver and digestive tract, suggesting a potential regulatory pathway from genome to phenotypes of energy metabolism and absorption via DNA methylation. Cross-sectional and longitudinal EWAS comparisons indicated different mechanisms between CpGs related to BMI and BMI change.</p><p><strong>Conclusion: </strong>This study enhances our understanding of the epigenetic dynamics underlying BMI change and emphasizes the value of longitudinal analyses in deciphering the complex interplay between epigenetics and obesity.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"16 1","pages":"70"},"PeriodicalIF":4.8,"publicationDate":"2024-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11131215/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141157375","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigating neonatal health risk variables through cell-type specific methylome-wide association studies.","authors":"Thomas L Campbell, Lin Y Xie, Ralen H Johnson, Christina M Hultman, Edwin J C G van den Oord, Karolina A Aberg","doi":"10.1186/s13148-024-01681-3","DOIUrl":"10.1186/s13148-024-01681-3","url":null,"abstract":"<p><p>Adverse neonatal outcomes are a prevailing risk factor for both short- and long-term mortality and morbidity in infants. Given the importance of these outcomes, refining their assessment is paramount for improving prevention and care. Here we aim to enhance the assessment of these often correlated and multifaceted neonatal outcomes. To achieve this, we employ factor analysis to identify common and unique effects and further confirm these effects using criterion-related validity testing. This validation leverages methylome-wide profiles from neonatal blood. Specifically, we investigate nine neonatal health risk variables, including gestational age, Apgar score, three indicators of body size, jaundice, birth diagnosis, maternal preeclampsia, and maternal age. The methylomic profiles used for this research capture data from nearly all 28 million methylation sites in human blood, derived from the blood spot collected from 333 neonates, within 72 h post-birth. Our factor analysis revealed two common factors, size factor, that captured the shared effects of weight, head size, height, and gestational age and disease factor capturing the orthogonal shared effects of gestational age, combined with jaundice and birth diagnosis. To minimize false positives in the validation studies, validation was limited to variables with significant cumulative association as estimated through an in-sample replication procedure. This screening resulted in that the two common factors and the unique effects for gestational age, jaundice and Apgar were further investigated with full-scale cell-type specific methylome-wide association analyses. Highly significant, cell-type specific, associations were detected for both common effect factors and for Apgar. Gene Ontology analyses revealed multiple significant biologically relevant terms for the five fully investigated neonatal health risk variables. Given the established links between adverse neonatal outcomes and both immediate and long-term health, the distinct factor effects (representing the common and unique effects of the risk variables) and their biological profiles confirmed in our work, suggest their potential role as clinical biomarkers for assessing health risks and enhancing personalized care.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"16 1","pages":"69"},"PeriodicalIF":5.7,"publicationDate":"2024-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11112760/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141080763","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Semimethylation is a feature of diffuse large B-cell lymphoma, and subgroups with poor prognosis are characterized by global hypomethylation and short telomere length.","authors":"Olivia Carlund, Elina Thörn, Pia Osterman, Maja Fors, Andy Dernstedt, Mattias N E Forsell, Martin Erlanson, Mattias Landfors, Sofie Degerman, Magnus Hultdin","doi":"10.1186/s13148-024-01680-4","DOIUrl":"10.1186/s13148-024-01680-4","url":null,"abstract":"<p><strong>Background: </strong>Large B-cell lymphoma (LBCL) is the most common lymphoma and is known to be a biologically heterogeneous disease regarding genetic, phenotypic, and clinical features. Although the prognosis is good, one-third has a primary refractory or relapsing disease which underscores the importance of developing predictive biological markers capable of identifying high- and low-risk patients. DNA methylation (DNAm) and telomere maintenance alterations are hallmarks of cancer and aging. Both these alterations may contribute to the heterogeneity of the disease, and potentially influence the prognosis of LBCL.</p><p><strong>Results: </strong>We studied the DNAm profiles (Infinium MethylationEPIC BeadChip) and relative telomere lengths (RTL) with qPCR of 93 LBCL cases: Diffuse large B-cell lymphoma not otherwise specified (DLBCL, n = 66), High-grade B-cell lymphoma (n = 7), Primary CNS lymphoma (n = 8), and transformation of indolent B-cell lymphoma (n = 12). There was a substantial methylation heterogeneity in DLBCL and other LBCL entities compared to normal cells and other B-cell neoplasms. LBCL cases had a particularly aberrant semimethylated pattern (0.15 ≤ β ≤ 0.8) with large intertumor variation and overall low hypermethylation (β > 0.8). DNAm patterns could not be used to distinguish between germinal center B-cell-like (GC) and non-GC DLBCL cases. In cases treated with R-CHOP-like regimens, a high percentage of global hypomethylation (β < 0.15) was in multivariable analysis associated with worse disease-specific survival (DSS) (HR 6.920, 95% CI 1.499-31.943) and progression-free survival (PFS) (HR 4.923, 95% CI 1.286-18.849) in DLBCL and with worse DSS (HR 5.147, 95% CI 1.239-21.388) in LBCL. These cases with a high percentage of global hypomethylation also had a higher degree of CpG island methylation, including islands in promoter-associated regions, than the cases with less hypomethylation. Additionally, telomere length was heterogenous in LBCL, with a subset of the DLBCL-GC cases accounting for the longest RTL. Short RTL was independently associated with worse DSS (HR 6.011, 95% CI 1.319-27.397) and PFS (HR 4.689, 95% CI 1.102-19.963) in LBCL treated with R-CHOP-like regimens.</p><p><strong>Conclusion: </strong>We hypothesize that subclones with high global hypomethylation and hypermethylated CpG islands could have advantages in tumor progression, e.g. by inactivating tumor suppressor genes or promoting treatment resistance. Our findings suggest that cases with high global hypomethylation and thus poor prognosis could be candidates for alternative treatment regimens including hypomethylating drugs.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"16 1","pages":"68"},"PeriodicalIF":5.7,"publicationDate":"2024-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11110316/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141075724","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DNA methylation and type 2 diabetes: a systematic review.","authors":"Nikhil Nadiger, Jyothisha Kana Veed, Priyanka Chinya Nataraj, Arpita Mukhopadhyay","doi":"10.1186/s13148-024-01670-6","DOIUrl":"10.1186/s13148-024-01670-6","url":null,"abstract":"<p><strong>Objective: </strong>DNA methylation influences gene expression and function in the pathophysiology of type 2 diabetes mellitus (T2DM). Mapping of T2DM-associated DNA methylation could aid early detection and/or therapeutic treatment options for diabetics.</p><p><strong>Design: </strong>A systematic literature search for associations between T2DM and DNA methylation was performed. Prospero registration ID: CRD42020140436.</p><p><strong>Methods: </strong>PubMed and ScienceDirect databases were searched (till October 19, 2023). Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and New Castle Ottawa scale were used for reporting the selection and quality of the studies, respectively.</p><p><strong>Result: </strong>Thirty-two articles were selected. Four of 130 differentially methylated genes in blood, adipose, liver or pancreatic islets (TXNIP, ABCG1, PPARGC1A, PTPRN2) were reported in > 1 study. TXNIP was hypomethylated in diabetic blood across ethnicities. Gene enrichment analysis of the differentially methylated genes highlighted relevant disease pathways (T2DM, type 1 diabetes and adipocytokine signaling). Three prospective studies reported association of methylation in IGFBP2, MSI2, FTO, TXNIP, SREBF1, PHOSPHO1, SOCS3 and ABCG1 in blood at baseline with incident T2DM/hyperglycemia. Sex-specific differential methylation was reported only for HOOK2 in visceral adipose tissue (female diabetics: hypermethylated, male diabetics: hypomethylated). Gene expression was inversely associated with methylation status in 8 studies, in genes including ABCG1 (blood), S100A4 (adipose tissue), PER2 (pancreatic islets), PDGFA (liver) and PPARGC1A (skeletal muscle).</p><p><strong>Conclusion: </strong>This review summarizes available evidence for using DNA methylation patterns to unravel T2DM pathophysiology. Further validation studies in diverse populations will set the stage for utilizing this knowledge for identifying early diagnostic markers and novel druggable pathways.</p>","PeriodicalId":10366,"journal":{"name":"Clinical Epigenetics","volume":"16 1","pages":"67"},"PeriodicalIF":5.7,"publicationDate":"2024-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11100087/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140956419","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}