Physical Activity Level Influences MTHFR Gene Methylation Profile in Diabetic Patients

Diniz, Tainá Gomes; Silva, Alexandre; Nunes, Mayara Karla dos Santos; Ribeiro, Mateus Duarte; Filho, João Aragão Ximenes; Nascimento, Rayner Anderson Ferreira do; Gomes, Cecília Neta Alves Pegado; Evangelista, Isabella; Oliveira, Naila Francis Paulo de; Persuhn, Darlene Camati

doi:10.3389/fphys.2020.618672

“…For example, hypermethylation of the MTHFR promoter has been described as a protective factor against ischemic stroke [ 72 ]. Moreover, it has been demonstrated that MTHFR demethylation is more frequent in subjects that are physically inactive [ 73 ], and that homocysteine can induce demethylation in the promoter region of the MTHFR gene in human vascular smooth muscle cells [ 74 ]. Recent studies have shown that MTHFR promoter methylation is also linked to circulating folate, vitamin B12, and homocysteine levels in individuals affected by Alzheimer's [ 75 ] and cardiovascular diseases [ 76 ], suggesting that the MTHFR methylation status could be a mediator of impairments of the folate metabolic pathway.…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial DNA and Epigenetics: Investigating Interactions with the One-Carbon Metabolism in Obesity

Bordoni

¹

,

Petracci

²

,

Młodzik-Czyżewska

³

et al. 2022

Oxidative Medicine and Cellular Longevity

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Mitochondrial DNA copy number (mtDNAcn) has been proposed for use as a surrogate biomarker of mitochondrial health, and evidence suggests that mtDNA might be methylated. Intermediates of the one-carbon cycle (1CC), which is duplicated in the cytoplasm and mitochondria, have a major role in modulating the impact of diet on the epigenome. Moreover, epigenetic pathways and the redox system are linked by the metabolism of glutathione (GSH). In a cohort of 101 normal-weight and 97 overweight/obese subjects, we evaluated mtDNAcn and methylation levels in both mitochondrial and nuclear areas to test the association of these marks with body weight, metabolic profile, and availability of 1CC intermediates associated with diet. Body composition was associated with 1CC intermediate availability. Reduced levels of GSH were measured in the overweight/obese group ( p = 1.3 ∗ 10 − 5 ). A high BMI was associated with lower LINE-1 ( p = 0.004 ) and nominally lower methylenetetrahydrofolate reductase (MTHFR) gene methylation ( p = 0.047 ). mtDNAcn was lower in overweight/obese subjects ( p = 0.004 ) and independently correlated with MTHFR methylation levels ( p = 0.005 ) but not to LINE-1 methylation levels ( p = 0.086 ). DNA methylation has been detected in the light strand but not in the heavy strand of the mtDNA. Although mtDNA methylation in the light strand did not differ between overweight/obese and normal-weight subjects, it was nominally correlated with homocysteine levels ( p = 0.035 ) and MTHFR methylation ( p = 0.033 ). This evidence suggests that increased body weight might perturb mitochondrial-nuclear homeostasis affecting the availability of nutrients acting as intermediates of the one-carbon cycle.

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“…In a diet-induced obesity model, Dnmt1 and Dnmt3a mRNA expression, described as an epigenetic mediator of insulin resistance, was elevated but could be significantly reduced after insulin treatment. 28 The DR severity and inflammatory pathways, 29 higher levels of total cholesterol and LDL cholesterol 30 and physical activity 31 were associated with MTHFR gene promoter hypermethylation.…”

Section: Discussionmentioning

confidence: 99%

DNA methyltransferase expression (DNMT1, DNMT3a and DNMT3b) as a potential biomarker for anti-VEGF diabetic macular edema response

Camacho

¹

,

Ribeiro

²

,

Pereira

³

et al. 2023

European Journal of Ophthalmology

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Purpose DNA methylation is involved in Diabetic Retinopathy progression showing a metabolic memory mechanism. However, the association of DNA methyltransferase with diabetic macular edema is still unknown. We aimed to describe the differences in DNA methyltransferase gene expression in patients with different diabetic macular edema responses. Methods A total of 27 diabetic patients, aged 59–90 years, were prospectively enrolled in this cross-sectional study. The participants were classified into control group (CG, n = 11), diabetic macular edema responders (rDME, n = 9) and non-responder diabetic macular edema (nrDME, n = 7) after anti-vascular endothelial growth factor (anti-VEGF) treatment. Only cases with a complete ophthalmological examination, digital 133° color fundus, and SD-OCT assessments were used. After RNA extraction and first-strand cDNA synthesis, quantitative real-time PCR was performed with specific primers on the CFX Connect™ Real-Time PCR Detection System to assess differential transcriptional expression patterns. Results The DNMT1 gene showed a positive correlation (r = 0.617; p = 0.043) with Best Corrected Visual Acuity (BCVA) in CG, a positive correlation (r = 0.917; p = 0.010) with HbA1c in nrDME and a negative correlation (r = −0.659; p = 0.049) with GCL-IPL thickness in rDME. DNMT3A gene showed a positive correlation (r = −0.890; p = 0.001) with Sub-foveal Choroidal thickness in rDME whereas DNMT3b gene showed a negative correlation (r = −0.815; p = 0.007) with HbA1c and RNFL (r = −0.664; p = 0.026) in CG. Conclusions Patients with similar metabolic profile risk factors showed associated DNA methyltransferase transcriptional expression patterns differences fitting with the anti-VEGF diabetic macular edema response. Further studies are needed to clarify if these results (1) reflect disease evolution, (2) translate the therapeutic impact, (3) or can help to predict the therapeutic resistance profile.

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“…The methylation profile is tissue-and site-specific, is associated with disease (Zhang, Lu, et al, 2020) and can be modulated by environmental factors such as UV radiation, nutrition, smoking, infection, physical activity, drugs, etc. (Corley et al, 2021;Costa et al, 2016;De Oliveira et al, 2020;Diniz et al, 2021;Esteller, 2017;Luna et al, 2018). It is important to mention that the VDR is expressed by oral cells (Ge et al, 2021), which makes the study of this gene in oral cells interesting, especially in the case of inflammation that affects the oral mucosa.…”

Section: Discussionmentioning

confidence: 99%

Polymorphism but not methylation status in the vitamin D receptor gene contributes to oral mucositis in children

Filho

¹

,

Souza

²

,

Coêlho

³

et al. 2022

Self Cite

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ObjectiveTo investigate the relationship between the polymorphisms rs1544410 (BsmI), rs2228570 (FokI) and rs731236 (TaqI) and DNA methylation status in the VDR gene (vitamin D receptor) with oral mucositis (OM) in oncopaediatric patients treated with methotrexate (MTX®).MethodsThe population comprised healthy patients with haematological malignancies aged between 5 and 19 years. An evaluation of oral conditions was performed using the Oral Assessment Guide. Demographic, clinical, biochemical and haematological data were obtained from medical records. Genomic DNA from oral mucosal cells was used for the analysis of polymorphisms (n = 102) (PCR‐restriction fragment length polymorphism) and DNA methylation (n = 81) (methylation‐specific PCR).ResultsMales predominated (57.8%), and the mean age was 10.3 years (±4.7). OM affected 84.3% of patients, of which 53.1% developed severe oral mucositis (SOM). Patients with OM had lower platelet and leukocyte counts (p < 0.05). The G allele of rs1544410 (p = 0.040) and the CT genotype of rs2228570 polymorphisms were associated with SOM (p = 0.038). A partially methylated status in the VDR promoter was found in all patients.ConclusionOM is associated with lower leukocyte and platelet counts. SOM is associated with the rs1544410 and rs2228570 polymorphisms. The methylation status of the VDR is not associated with inflammation or exposure to MTX®.

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Physical Activity Level Influences MTHFR Gene Methylation Profile in Diabetic Patients

Cited by 9 publications

References 38 publications

Mitochondrial DNA and Epigenetics: Investigating Interactions with the One-Carbon Metabolism in Obesity

Mitochondrial DNA and Epigenetics: Investigating Interactions with the One-Carbon Metabolism in Obesity

DNA methyltransferase expression (DNMT1, DNMT3a and DNMT3b) as a potential biomarker for anti-VEGF diabetic macular edema response

Polymorphism but not methylation status in the vitamin D receptor gene contributes to oral mucositis in children

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