Abstract:
BACKGROUND:Preterm birth (PTB), defined as child birth before completion of 37 weeks of gestation, is a major challenge in perinatal health care and can bear long-term medical and financial burden. Over a million children die each year due to PTB complications, and those who survive can face developmental delays. Unfortunately, our understanding of the molecular pathways associated with PTB remains limited. There is a growing body of evidence suggesting the role of DNA methylation (DNAm) in mediating the effects of PTB on future health outcomes. Thus, epigenome-wide association studies (EWAS), where DNAm sites are examined for associations with PTB, can help shed light on the biological mechanisms linking the two. RESULTS:In an Asian cohort of 1019 infants (68 preterm, 951 full term), we examined and compared the associations between PTB and genome-wide DNAm profiles using both cord tissue (n = 1019) and cord blood (n = 332) samples on Infinium HumanMethylation450 arrays. PTB was significantly associated (P < 5.8e-7) with DNAm at 296 CpGs (209 genes) in the cord blood. Over 95% of these CpGs were replicated in other PTB/gestational age EWAS conducted in (cord) blood. This replication was apparent even across populations of different ethnic origin (Asians, Caucasians, and African Americans). More than a third of these 296 CpGs were replicated in at least 4 independent studies, thereby identifying a robust set of PTB-linked epigenetic signatures in cord blood. Interrogation of cord tissue in addition to cord blood provided novel insights into the epigenetic status of the neonates born preterm. Overall, 994 CpGs (608 genes, P < 3.7e-7) associated with PTB in cord tissue, of which only 10 of these CpGs were identified in the analysis using cord blood. Genes from cord tissue showed enrichment of molecular pathways related to fetal growth and development, while those from cord blood showed enrichment of immune response pathways. A substantial number of PTB-associated CpGs from both the birth tissues were also associated with gestational age. CONCLUSIONS:Our findings provide insights into the epigenetic landscape of neonates born preterm, and that its status is captured more comprehensively by interrogation of more than one neonatal tissue in tandem. Both these neonatal tissues are clinically relevant in their unique ways and require careful consideration in identification of biomarkers related to PTB and gestational age. TRIAL REGISTRATION:This birth cohort is a prospective observational study designed to study the developmental origins of health and disease, and was retrospectively registered on 1 July 2010 under the identifier NCT01174875 .
journal_name
Clin Epigeneticsjournal_title
Clinical epigeneticsauthors
Wu Y,Lin X,Lim IY,Chen L,Teh AL,MacIsaac JL,Tan KH,Kobor MS,Chong YS,Gluckman PD,Karnani Ndoi
10.1186/s13148-018-0599-4subject
Has Abstractpub_date
2019-02-11 00:00:00pages
26issue
1eissn
1868-7075issn
1868-7083pii
10.1186/s13148-018-0599-4journal_volume
11pub_type
杂志文章abstract:BACKGROUND:The DNA modification 5-hydroxymethylcytosine (5hmC) is now referred to as the sixth base of DNA with evidence of tissue-specific patterns and correlation with gene regulation and expression. This epigenetic mark was recently reported as a potential biomarker for multiple types of cancer, but its application ...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-017-0368-9
更新日期:2017-07-14 00:00:00
abstract:BACKGROUND:Splicing is more efficient when coupled with transcription and it has been proposed that nucleosomes enriched in exons are important for splice site recognition. Lynch syndrome is a familial cancer syndrome that can be caused by the autosomal dominant inheritance of splice site mutations in the MutL homolog ...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-014-0032-6
更新日期:2014-12-13 00:00:00
abstract:BACKGROUND:Colorectal cancer (CRC) screening can effectively reduce disease-related mortality by detecting CRC at earlier stages. We have previously demonstrated that the presence of SDC2 methylation in stool DNA is significantly associated with the occurrence of CRC regardless of clinical stage. The aim of this study ...
journal_title:Clinical epigenetics
pub_type: 临床试验,杂志文章
doi:10.1186/s13148-019-0642-0
更新日期:2019-03-15 00:00:00
abstract:Background:New efficient therapies for urothelial carcinoma (UC) are urgently required. Small-molecule drugs targeting chromatin regulators are reasonable candidates because these regulators are frequently mutated or deregulated in UC. Indeed, in previous work, Romidepsin, which targets class I histone deacetylases (HD...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-017-0434-3
更新日期:2018-01-04 00:00:00
abstract:BACKGROUND:Epigenetic mechanisms have been suggested to play a role in the development of post-traumatic stress disorder (PTSD). Here, blood-derived DNA methylation data (HumanMethylation450 BeadChip) collected prior to and following combat exposure in three cohorts of male military members were analyzed to assess whet...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-019-0798-7
更新日期:2020-01-13 00:00:00
abstract:BACKGROUND:Identifying subjects with a high risk of ischemic stroke is fundamental for prevention of the disease. Both genetic and environmental risk factors contribute to ischemic stroke, but the underlying epigenetic mechanisms which mediate genetic and environmental risk effects are not fully understood. The aim of ...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-019-0784-0
更新日期:2019-12-10 00:00:00
abstract:BACKGROUND:B vitamins in the one-carbon metabolism pathway (folate, vitamin B6, and vitamin B12) have been implicated in DNA methylation, and their deficiency may contribute to cognitive decline through increased homocysteine (Hcy) levels and subsequent oxidative damage. The aim of this study was to investigate whether...
journal_title:Clinical epigenetics
pub_type: 临床试验,杂志文章
doi:10.1186/s13148-019-0741-y
更新日期:2019-10-11 00:00:00
abstract:BACKGROUND:Activation of transcription enhancers, especially super-enhancers, is one of the critical epigenetic features of tumorigenesis. However, very few studies have systematically identified the enhancers specific in cancer tissues. METHODS:Here, we studied the change of histone modifications in MMTV-PyVT breast ...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-019-0645-x
更新日期:2019-03-12 00:00:00
abstract::Heterozygous mutation of the transcription factor HNF1B is the most common cause of monogenetic developmental renal disease. Disease-associated mutations fall into two categories: HNF1B intragenic mutations and a 1.3 Mb deletion at chromosome 17q12. An increase in neurodevelopmental disorders has been observed in indi...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-018-0530-z
更新日期:2018-07-18 00:00:00
abstract:Background:Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease of the lungs that is currently the fourth leading cause of death worldwide. Genetic factors account for only a small amount of COPD risk, but epigenetic mechanisms, including DNA methylation, have the potential to mediate the interaction...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-018-0464-5
更新日期:2018-03-05 00:00:00
abstract:BACKGROUND:DNA methylation is a well-studied epigenetic mark that is frequently altered in diseases such as cancer, where specific changes are known to reflect the type and severity of the disease. Therefore, there is a growing interest in assessing the clinical utility of DNA methylation as a biomarker for diagnosing ...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-020-00880-y
更新日期:2020-06-22 00:00:00
abstract:BACKGROUND:Goblet cell metaplasia, a common feature of chronic obstructive pulmonary disease (COPD), is associated with mucus hypersecretion which contributes to the morbidity and mortality among patients. Transcription factors SAM-pointed domain-containing Ets-like factor (SPDEF) and forkhead box protein A2 (FOXA2) re...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-017-0341-7
更新日期:2017-04-24 00:00:00
abstract:BACKGROUND:Type 2 diabetes mellitus (T2D) is highly prevalent in Middle-Eastern and North African Arab populations, but the molecular basis for this susceptibility is unknown. Altered DNA methylation levels were reported in insulin-secreting and responding tissues, but whether methylation in accessible tissues such as ...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-015-0069-1
更新日期:2015-03-28 00:00:00
abstract:BACKGROUND:Compared to healthy individuals, those with stably repressed HIV experience a higher risk of developing insulin resistance, a hallmark of pre-diabetes and a major determinant for cardiometabolic diseases. Although epigenetic processes, including in particular DNA methylation, appear to be dysregulated in ind...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-019-0694-1
更新日期:2019-06-28 00:00:00
abstract:BACKGROUND:A key focus in cancer research is the discovery of biomarkers that accurately diagnose early lesions in non-invasive tissues. Several studies have identified malignancy-associated DNA methylation changes in blood, yet no general cancer biomarker has been identified to date. Here, we explore the potential of ...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-016-0172-y
更新日期:2016-01-20 00:00:00
abstract:Background:This study was aimed at understanding whether bronchial biopsy specimen can be used as a surrogate for DNA methylation analysis in surgically resected lung cancer. Methods:A genome-wide methylation was analyzed in 42 surgically resected tumor tissues, 136 bronchial washing, 12 sputum, and 8 bronchial biopsy...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-017-0432-5
更新日期:2017-12-20 00:00:00
abstract:BACKGROUND:Cancer treatments have substantially improved childhood cancer survival but are accompanied by long-term complications, notably chronic inflammatory diseases. We hypothesize that cancer treatments could lead to long-term epigenetic changes in immune cells, resulting in increased prevalence of inflammatory di...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-018-0561-5
更新日期:2018-11-06 00:00:00
abstract:BACKGROUND:About half of all prostate cancers harbor the TMPRSS2:ERG (T2E) gene fusion. While T2E-positive and T2E-negative tumors represent specific molecular subtypes of prostate cancer (PCa), previous studies have not yet comprehensively investigated how these tumor subtypes differ at the epigenetic level. We theref...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-015-0161-6
更新日期:2015-12-12 00:00:00
abstract:BACKGROUND:The current epidemic of obesity and associated diseases calls for swift actions to better understand the mechanisms by which genetics and environmental factors affect metabolic health in humans. Monozygotic (MZ) twin pairs showing discordance for obesity suggest that epigenetic influences represent one such ...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-015-0073-5
更新日期:2015-04-02 00:00:00
abstract:BACKGROUND:Prostate cancer (PC) is a commonly diagnosed malignancy in males, especially in the western hemisphere. The extensive use of multiple biomarkers plays an important role in the diagnosis and prognosis of PC. However, the accuracy of biomarkers for PC prognosis needs to be urgently improved. This study aimed t...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-019-0693-2
更新日期:2019-07-09 00:00:00
abstract:BACKGROUND:Both forms of facioscapulohumeral muscular dystrophy (FSHD) are associated with aberrant epigenetic regulation of the chromosome 4q35 D4Z4 macrosatellite. Chromatin changes due to large deletions of heterochromatin (FSHD1) or mutations in chromatin regulatory proteins (FSHD2) lead to relaxation of epigenetic...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-015-0072-6
更新日期:2015-03-29 00:00:00
abstract:: Friedreich ataxia (FRDA) is a debilitating and frequently fatal neurological disorder that is recessively inherited. It belongs to the group of genetic disorders known as the Repeat Expansion Diseases, in which pathology arises from the deleterious consequences of the inheritance of a tandem repeat array whose repeat...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/1868-7083-4-2
更新日期:2012-01-30 00:00:00
abstract:BACKGROUND:Smoking is the largest preventable cause of morbidity and mortality in the United States. In previous work, we demonstrated that altered DNA methylation at the aryl hydrocarbon receptor repressor (AHRR) is correlated with self-reported smoking in 19-year-old African Americans with relatively low levels of sm...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/1868-7083-5-19
更新日期:2013-10-11 00:00:00
abstract:Background:AXL is one of the TAM (TYRO3, AXL and MERTK) receptor tyrosine kinases and may affect numerous immune-related health conditions. However, the role for AXL in asthma, including its epigenetic regulation, has not been extensively studied. Methods:We investigated the association between AXL DNA methylation at ...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-017-0421-8
更新日期:2017-11-07 00:00:00
abstract:BACKGROUND:In vitro follicle culture (IFC), as applied in the mouse system, allows the growth and maturation of a large number of immature preantral follicles to become mature and competent oocytes. In the human oncofertility clinic, there is increasing interest in developing this technique as an alternative to ovarian...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-019-0794-y
更新日期:2019-12-19 00:00:00
abstract:BACKGROUND:Inadequate maternal nutrition during early fetal development can create permanent alterations in the offspring, leading to poor health outcomes. While nutrients involved in one-carbon cycle metabolism are important to fetal growth, associations with specific nutrients remain inconsistent. This study estimate...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-016-0174-9
更新日期:2016-01-22 00:00:00
abstract:BACKGROUNDS:Colorectal cancer (CRC) results from the accumulation of epigenetic and genetic changes in colon cells during neoplasic transformation, which the activation of Wingless (Wnt) signaling pathway is a common mechanism for CRC initiation. The Wnt pathway is mainly regulated by Wnt antagonists, as secreted frizz...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-020-00875-9
更新日期:2020-06-09 00:00:00
abstract:BACKGROUND:Modification of DNA by methylation of cytosines at CpG dinucleotides is a widespread phenomenon that leads to changes in gene expression, thereby influencing and regulating many biological processes. Recent technical advances in the genome-wide determination of single-base DNA-methylation enabled epigenome-w...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-014-0040-6
更新日期:2015-01-22 00:00:00
abstract:BACKGROUND:Despite the significant global loss of DNA hydroxymethylation marks in prostate cancer tissues, the locus-specific role of hydroxymethylation in prostate tumorigenesis is unknown. We characterized hydroxymethylation and methylation marks by performing whole-genome next-generation sequencing in representative...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-016-0195-4
更新日期:2016-03-15 00:00:00
abstract:BACKGROUND:Kawasaki disease (KD) is a prevalent pediatric disease worldwide and can cause coronary artery aneurysm as a severe complication. Typically, DNA methylation is thought to repress the expression of nearby genes. However, the cases in which DNA methylation promotes gene expression have been reported. In additi...
journal_title:Clinical epigenetics
pub_type: 杂志文章
doi:10.1186/s13148-018-0557-1
更新日期:2018-11-01 00:00:00