ArticleMolecular medicine (Cambridge, Mass.)2020
DNA methylation microarrays identify epigenetically regulated lipid related genes in obese patients with hypercholesterolemia.
Article in Molecular medicine (Cambridge, Mass.), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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15 citing papers in PubMed, 27 citations in OpenAlex.
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- Unraveling novel mechanisms of ATP-Binding cassette (ABC) transporter in insulin Resistance-induced amyloidogenesis.Metabolic brain disease · 2025Review
- Association analysis between an epigenetic alcohol risk score and blood pressure.Clinical epigenetics · 2024Article
- Association analysis between an epigenetic risk score and blood pressure.Research square · 2024Article
- Association analysis between an epigenetic alcohol risk score and blood pressure.medRxiv : the preprint server for health sciences · 2024Article
- Methylation changes of liver DNA during the formation of gallstones.Epigenomics · 2024Article
- Integrative network analysis of differentially methylated regions to study the impact of gestational weight gain on maternal metabolism and fetal-neonatal growth.Genetics and molecular biology · 2024Article
- Methylation status ofEpigenomics · 2024Article
- Expression Variation ofInternational journal of molecular sciences · 2023Article
- A Mixture of Endocrine Disrupting Chemicals Associated with Lower Birth Weight in Children Induces Adipogenesis and DNA Methylation Changes in Human Mesenchymal Stem Cells.International journal of molecular sciences · 2022Article
- Lysosomal acid lipase deficiency: A rare inherited dyslipidemia but potential ubiquitous factor in the development of atherosclerosis and fatty liver disease.Frontiers in genetics · 2022Review
- Role of adaptin protein complexes in intracellular trafficking and their impact on diseases.Bioengineered · 2021Article
- Lipid Phenotypes and DNA Methylation: a Review of the Literature.Current atherosclerosis reports · 2021Review
- Hyperlipidemia May Synergize with Hypomethylation in Establishing Trained Immunity and Promoting Inflammation in NASH and NAFLD.Journal of immunology research · 2021Article
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12 authors at 2 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
backgroundEpigenetics can contribute to lipid disorders in obesity. The DNA methylation pattern can be the cause or consequence of high blood lipids. The aim of the study was to investigate the DNA methylation profile in peripheral leukocytes associated with elevated LDL-cholesterol level in overweight and obese individuals.
methodsTo identify the differentially methylated genes, genome-wide DNA methylation microarray analysis was performed in leukocytes of obese individuals with high LDL-cholesterol (LDL-CH, ≥ 3.4 mmol/L) versus control obese individuals with LDL-CH, < 3.4 mmol/L. Biochemical tests such as serum glucose, total cholesterol, HDL cholesterol, triglycerides, insulin, leptin, adiponectin, FGF19, FGF21, GIP and total plasma fatty acids content have been determined. Oral glucose and lipid tolerance tests were also performed. Human DNA Methylation Microarray (from Agilent Technologies) containing 27,627 probes for CpG islands was used for screening of DNA methylation status in 10 selected samples. Unpaired t-test and Mann-Whitney U-test were used for biochemical and anthropometric parameters statistics. For microarrays analysis, fold of change was calculated comparing hypercholesterolemic vs control group. The q-value threshold was calculated using moderated Student's t-test followed by Benjamini-Hochberg multiple test correction FDR.
resultsIn this preliminary study we identified 190 lipid related CpG loci differentially methylated in hypercholesterolemic versus control individuals. Analysis of DNA methylation profiles revealed several loci engaged in plasma lipoprotein formation and metabolism, cholesterol efflux and reverse transport, triglycerides degradation and fatty acids transport and β-oxidation. Hypermethylation of CpG loci located in promoters of genes regulating cholesterol metabolism: PCSK9, LRP1, ABCG1, ANGPTL4, SREBF1 and NR1H2 in hypercholesterolemic patients has been found. Novel epigenetically regulated CpG sites include ABCG4, ANGPTL4, AP2A2, AP2M1, AP2S1, CLTC, FGF19, FGF1R, HDLBP, LIPA, LMF1, LRP5, LSR, NR1H2 and ZDHHC8 genes.
conclusionsOur results indicate that obese individuals with hypercholesterolemia present specific DNA methylation profile in genes related to lipids transport and metabolism. Detailed knowledge of epigenetic regulation of genes, important for lipid disorders in obesity, underlies the possibility to influence target genes by changing diet and lifestyle, as DNA methylation is reversible and depends on environmental factors. These findings give rise for further studies on factors that targets methylation of revealed genes.
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