ArticlePloS one2020
DNA methylation patterns of LINE-1 and Alu for pre-symptomatic dementia in type 2 diabetes.
Article in PloS one, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 20 citations in OpenAlex.
- Research Progress on Pathology, Molecular Mechanisms, and Intervention Strategies of Cognitive Dysfunction Associated with Type 2 Diabetes.International journal of general medicine · 2026Review
- Extrachromosomal Circular DNA and Transposable Elements in Type 2 Diabetes.International journal of molecular sciences · 2025Review
- Genome-wide DNA methylation profiles of colorectal tumors in Lynch syndrome and familial adenomatous polyposis.Clinical epigenetics · 2025Article
- LINE-1 Methylation sustains telomere length in pregnant women: effects on pregnancy failure.Clinical epigenetics · 2025Article
- Article
- Exploring the Interconnections of Genetic, Lifestyle, and Epigenetic Influences on Brain Aging: A Comprehensive Review.Current Alzheimer research · 2025Review
- Retrotransposons and Diabetes Mellitus.Epigenomes · 2024Review
- Epigenetic role of LINE-1 methylation and key genes in pregnancy maintenance.Scientific reports · 2024Article
- Decreased Alu methylation in type 2 diabetes mellitus patients increases HbA1c levels.Journal of clinical laboratory analysis · 2023Article
- Quadrato Motor Training (QMT) is associated with DNA methylation changes at DNA repeats: A pilot study.PloS one · 2023Article
- LINE-1 and Alu methylation signatures in autism spectrum disorder and their associations with the expression of autism-related genes.Scientific reports · 2022Article
- Particulate matter-induced hypomethylation of Alu and LINE1 in normal human bronchial epithelial cells and epidermal keratinocytes.Genes and environment : the official journal of the Japanese Environmental Mutagen Society · 2022Article
- Are we getting closer to the role of one-carbon metabolism and methylation in the onset of Down syndrome?Human cell · 2022Article
- The critical role of epigenetic mechanism in PMGenes and environment : the official journal of the Japanese Environmental Mutagen Society · 2021Review
- Lamivudine improves cognitive decline in SAMP8 mice: Integrating in vivo pharmacological evaluation and network pharmacology.Journal of cellular and molecular medicine · 2021Article
- Losing DNA methylation at repetitive elements and breaking bad.Epigenetics & chromatin · 2021Review
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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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