For Publishers
DiscoveryMetadataPeer reviewHostingPublishing
For Researchers
JoinPublishReviewCollect
Register
Blog
About
Search
Advanced search
My ScienceOpen
Search
For Publishers
For Researchers
Blog
About
7
views
39
references
 Top references
cited by
10
    
0 reviews
 Review
0
comments
 Comment
0
recommends
+1 Recommend
0 collections
    0
    shares
      201
      similar
       All similar
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      The shortening of leukocyte telomere length relates to DNA hypermethylation of LINE-1 in type 2 diabetes mellitus

      research-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Background

          We aim to investigate the cross-talking of leukocyte telomere length (LTL) and DNA methylation of LINE-1 in type 2 diabetes mellitus (T2DM).

          Results

          LTL (ratio of the copy number of telomere [T] repeats to that of a single [S] gene) was significantly shortened in T2DM compared with controls (0.94 ± 0.41 vs. 1.14 ± 0.48, P < 0.001), and decreased steadily with age in both controls and T2DM. Conversely, significant increase of LINE-1 DNA methylation was found in T2DM compared with controls (49.60 ± 14.55 vs. 37.81 ± 9.07, P < 0.001). Moreover, age, HbA1c, and LINE-1 methylation ratio were stably negatively related with LTL after multi-adjustment. Shorter LTL was associated with an increased risk of T2DM [adjusted OR (95% CI) = 2.458 (1.192, 5.070), P = 0.015], while lower LINE-1 DNA methylation levels could reduce the risk of T2DM [adjusted OR (95% CI) = 0.189 (0.089, 0.400), P < 0.001].

          Materials and Methods

          We performed a hospital-based case–control study of 205 T2DM patients and 213 subjects of healthy control with sex and age matched. LTL and DNA methylation of LINE-1 was measured by quantitative PCR and quantitative methylation-specific PCR (qMSP), respectively.

          Conclusions

          Our research demonstrates the association between shorter LTL and LINE-1 hyper-methylation in Chinese T2DM patients. These findings suggest that shorter LTL might be associated with T2DM in a manner dependent of epigenetic level.

          Related collections

          Most cited references39

          • Record: found
          • Abstract: found
          • Article: not found

          A simple method for estimating global DNA methylation using bisulfite PCR of repetitive DNA elements.

          Allen Yang, Marcos R H Estécio, Ketan Doshi … (2004)
          We report a method for studying global DNA methylation based on using bisulfite treatment of DNA and simultaneous PCR of multiple DNA repetitive elements, such as Alu elements and long interspersed nucleotide elements (LINE). The PCR product, which represents a pool of approximately 15 000 genomic loci, could be used for direct sequencing, selective restriction digestion or pyrosequencing, in order to quantitate DNA methylation. By restriction digestion or pyrosequencing, the assay was reproducible with a standard deviation of only 2% between assays. Using this method we found that almost two-thirds of the CpG methylation sites in Alu elements are mutated, but of the remaining methylation target sites, 87% were methylated. Due to the heavy methylation of repetitive elements, this assay was especially useful in detecting decreases in DNA methylation, and this assay was validated by examining cell lines treated with the methylation inhibitor 5-aza-2'deoxycytidine (DAC), where we found a 1-16% decrease in Alu element and 18-60% LINE methylation within 3 days of treatment. This method can be used as a surrogate marker of genome-wide methylation changes. In addition, it is less labor intensive and requires less DNA than previous methods of assessing global DNA methylation.
          Article 0 comments Cited 279 times – based on 0 reviews     Review now
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            The epigenetic regulation of mammalian telomeres.

            Maria Blasco (2007)
            Increasing evidence indicates that chromatin modifications are important regulators of mammalian telomeres. Telomeres provide well studied paradigms of heterochromatin formation in yeast and flies, and recent studies have shown that mammalian telomeres and subtelomeric regions are also enriched in epigenetic marks that are characteristic of heterochromatin. Furthermore, the abrogation of master epigenetic regulators, such as histone methyltransferases and DNA methyltransferases, correlates with loss of telomere-length control, and telomere shortening to a critical length affects the epigenetic status of telomeres and subtelomeres. These links between epigenetic status and telomere-length regulation provide important new avenues for understanding processes such as cancer development and ageing, which are characterized by telomere-length defects.
            Article 0 comments Cited 200 times – based on 0 reviews     Review now
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              DNA methyltransferases control telomere length and telomere recombination in mammalian cells.

              Susana Gonzalo, Isabel Jaco, Mario Fraga … (2006)
              Here, we describe a role for mammalian DNA methyltransferases (DNMTs) in telomere length control. Mouse embryonic stem (ES) cells genetically deficient for DNMT1, or both DNMT3a and DNMT3b have dramatically elongated telomeres compared with wild-type controls. Mammalian telomere repeats (TTAGGG) lack the canonical CpG methylation site. However, we demonstrate that mouse subtelomeric regions are heavily methylated, and that this modification is decreased in DNMT-deficient cells. We show that other heterochromatic marks, such as histone 3 Lys 9 (H3K9) and histone 4 Lys 20 (H4K20) trimethylation, remain at both subtelomeric and telomeric regions in these cells. Lack of DNMTs also resulted in increased telomeric recombination as indicated by sister-chromatid exchanges involving telomeric sequences, and by the presence of 'alternative lengthening of telomeres' (ALT)-associated promyelocytic leukaemia (PML) bodies (APBs). This increased telomeric recombination may lead to telomere-length changes, although our results do not exclude a potential involvement of telomerase and telomere-binding proteins in the aberrant telomere elongation observed in DNMT-deficient cells. Together, these results demonstrate a previously unappreciated role for DNA methylation in maintaining telomere integrity.
              Article 0 comments Cited 176 times – based on 0 reviews     Review now
                Bookmark
                All references

                Author and article information

                Journal
                Journal ID (nlm-ta): Oncotarget
                Journal ID (iso-abbrev): Oncotarget
                Journal ID (publisher-id): Oncotarget
                Journal ID (publisher-id): ImpactJ
                Title: Oncotarget
                Publisher: Impact Journals LLC
                ISSN (Electronic): 1949-2553
                Publication date Collection: 26 September 2017
                Publication date (Electronic): 22 May 2017
                Volume: 8
                Issue: 43
                Pages: 73964-73973
                Affiliations
                1 Department of Clinical Laboratory, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
                2 Department of Clinical Laboratory, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, 100730, China
                3 Department of Cardiology, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou 325027, Zhejiang, China
                4 Department of Genetics, Albert Einstein College of Medicine, Bronx, NY 10461, USA
                Author notes
                Correspondence to: Wei Cui, wendycuiwei@ 123456sina.cn
                Article
                Publisher ID: 18167
                DOI: 10.18632/oncotarget.18167
                PMC ID: 5650315
                SO-VID: a41af835-1388-47bc-8e0d-a5ded248175a
                Copyright © Copyright: © 2017 Wu et al.
                License:

                This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                Date received : 04 April 2017
                Date accepted : 11 May 2017
                Categories
                Subject: Research Paper

                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: type 2 diabetes mellitus,leukocyte telomere length,dna methylation,line-1,glycated hemoglobin
                Data availability:
                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: type 2 diabetes mellitus, leukocyte telomere length, dna methylation, line-1, glycated hemoglobin

                Comments

                Comment on this article

                scite_

                Similar content201

                See all similar

                Cited by10

                See all cited by

                Most referenced authors1,674

                See all reference authors