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DNA methylation patterns of LINE-1 and Alu for pre-symptomatic dementia in type 2 diabetes

Sae-Lee, Chanachai, Biasi, Julien De, Robinson, Natassia, Barrow, Timothy M, Mathers, John, Koutsidis, Georgios and Byun, Hyang-Min (2020) DNA methylation patterns of LINE-1 and Alu for pre-symptomatic dementia in type 2 diabetes. PLOS ONE, 15 (6). e0234578. ISSN 1932-6203

Item Type: Article


The identification of early markers of dementia is important for higher-risk populations such as those with type 2 diabetes (T2D). Retrotransposons, including long interspersed nuclear element 1 (LINE-1) and Alu, comprise ~40% of the human genome. Although dysregulation of these retrotransposons can induce aberrant gene regulation and genomic instability, their role in the development of pre-symptomatic dementia (PSD) among T2D patients is unknown. Here, we examined locus-specific changes in LINE-1 and Alu methylation in PSD and the potential to offset these changes via supplementation with folate and vitamin B12. We interrogated DNA methylation patterns corresponding to 22,352 probes for LINE-1 and Alu elements using publicly-available Illumina Infinium 450K methylation datasets from i) an 18-month prospective study in 28 T2D patients (GSE62003) and ii) an intervention study in which 44 individuals were supplemented with folic acid (400 μg/day) and vitamin B12 (500 μg/day) over two years (GSE74548). We identified 714 differentially methylated positions (DMP) mapping to retrotransposons in T2D patients who developed PSD in comparison to those who did not (PFDR < 0.05), comprised of 2.4% (228 probes) of all LINE-1 probes and 3.8% (486 probes) of all Alu probes. These loci were enriched in genes with functions related to Alzheimer's disease and cognitive decline, including GNB5, GNG7 and PKN3 (p < 0.05). In older individuals supplemented with folate/vitamin B12, 85 (11.9%) PSD retrotransposon loci showed significant changes in methylation (p < 0.05): participants with the MTHFR CC genotype predominantly showed hypermethylation at these loci, while hypomethylation was observed more frequently in those with the TT genotype. In T2D patients, LINE-1 and Alu elements are differentially methylated in PSD in a locus-specific manner and may offer clinical utility in monitoring risk of dementia. Further work is required to examine the potential for dietary supplementation in lowering the risk of PSD.

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Additional Information: ** From PLOS via Jisc Publications Router ** History: collection 2020; received 24-01-2020; accepted 28-05-2020; epub 11-06-2020. ** Licence for this article:
Uncontrolled Keywords: Research Article, Biology and life sciences, Medicine and health sciences, Physical sciences
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Item ID: 12122
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ISSN: 1932-6203
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ORCID for Chanachai Sae-Lee: ORCID iD
ORCID for Timothy M Barrow: ORCID iD

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Date Deposited: 23 Jun 2020 08:57
Last Modified: 30 Sep 2020 11:01


Author: Chanachai Sae-Lee ORCID iD
Author: Timothy M Barrow ORCID iD
Author: Julien De Biasi
Author: Natassia Robinson
Author: John Mathers
Author: Georgios Koutsidis
Author: Hyang-Min Byun
Editor: Ruslan Kalendar

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Faculty of Health Sciences and Wellbeing > School of Nursing and Health Sciences

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