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

Autor: Georgios Koutsidis, Natassia Robinson, Julien De Biasi, Timothy M. Barrow, Chanachai Sae-Lee, Hyang-Min Byun, John C. Mathers
Přispěvatelé: Kalendar, Ruslan
Jazyk: angličtina
Rok vydání: 2020
Předmět:
0301 basic medicine
B Vitamins
Male
Retrotransposon
Alzheimer's Disease
Biochemistry
0302 clinical medicine
Mobile Genetic Elements
Genotype
Medicine and Health Sciences
Cognitive decline
Genetics
Aged
80 and over
Multidisciplinary
DNA methylation
biology
Organic Compounds
Neurodegenerative Diseases
Methylation
Genomics
Vitamins
Middle Aged
Chromatin
Nucleic acids
Chemistry
Retrotransposons
Neurology
Physical Sciences
Medicine
Epigenetics
Female
DNA modification
Chromatin modification
Research Article
Chromosome biology
Cell biology
Science
Alu element
Cobalamins
03 medical and health sciences
Genetic Elements
Folic Acid
Alu Elements
Mental Health and Psychiatry
Humans
Repeated Sequences
Aged
Biology and life sciences
Organic Chemistry
Transposable Elements
Chemical Compounds
DNA
Long interspersed nuclear element
030104 developmental biology
Long Interspersed Nucleotide Elements
Diabetes Mellitus
Type 2
Genetic Loci
Methylenetetrahydrofolate reductase
Asymptomatic Diseases
biology.protein
Dementia
Gene expression
030217 neurology & neurosurgery
Zdroj: PLoS ONE
PLoS ONE, Vol 15, Iss 6, p e0234578 (2020)
ISSN: 1932-6203
Popis: 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.
Databáze: OpenAIRE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje