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Impact of Consuming Extra-Virgin Olive Oil or Nuts within a Mediterranean Diet on DNA Methylation in Peripheral White Blood Cells within the PREDIMED-Navarra Randomized Controlled Trial: A Role for Dietary Lipids.
Arpón, A, Milagro, FI, Razquin, C, Corella, D, Estruch, R, Fitó, M, Marti, A, Martínez-González, MA, Ros, E, Salas-Salvadó, J, et al
Nutrients. 2017;10(1)
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Plain language summary
Our genes are not fixed. They interact constantly with the environment through dietary and lifestyle factors, which affect whether genes are expressed or not. This is often referred to as epigenetic modulation. DNA methylation is an epigenetic mechanism that adds a methyl group to DNA, thereby modifying the function of the genes and affecting gene expression. Epigenetic alterations have been associated with conditions, such as obesity, type 2 diabetes, cardiovascular disease and immunological conditions. It is suggested that epigenetic marks are reversible and can be modulated by nutrient status and certain dietary components. The aim of the current study was to explore methylation changes in genes of peripheral white blood cells in a subset of participants from the PREDIMED-Navarra randomised controlled trial. 36 participants were allocated to three groups, all consuming a Mediterranean diet. In the first group, the diet was supplemented with extra virgin olive oil (EVOO), in the second group, with mixed nuts, and the third group, which served as the control group, were advised to consume a low-fat diet. Changes in DNA methylation were analysed from blood samples at baseline and at five-year follow-up. The authors observed methylation changes in several genes, related to metabolism, glucose and energy regulation, diabetes and inflammation, after the consumption of EVOO and nuts. They concluded that the beneficial effects of Mediterranean diets that include EVOO and nuts, may, at least in part, be mediated via epigenetic mechanisms. As these foods are high in monounsaturated and polyunsaturated fats, the quality of fat may be playing an important role in this mediation.
Abstract
DNA methylation could be reversible and mouldable by environmental factors, such as dietary exposures. The objective was to analyse whether an intervention with two Mediterranean diets, one rich in extra-virgin olive oil (MedDiet + EVOO) and the other one in nuts (MedDiet + nuts), was influencing the methylation status of peripheral white blood cells (PWBCs) genes. A subset of 36 representative individuals were selected within the PREvención con DIeta MEDiterránea (PREDIMED-Navarra) trial, with three intervention groups in high cardiovascular risk volunteers: MedDiet + EVOO, MedDiet + nuts, and a low-fat control group. Methylation was assessed at baseline and at five-year follow-up. Ingenuity pathway analysis showed routes with differentially methylated CpG sites (CpGs) related to intermediate metabolism, diabetes, inflammation, and signal transduction. Two CpGs were specifically selected: cg01081346-CPT1B/CHKB-CPT1B and cg17071192-GNAS/GNASAS, being associated with intermediate metabolism. Furthermore, cg01081346 was associated with PUFAs intake, showing a role for specific fatty acids on epigenetic modulation. Specific components of MedDiet, particularly nuts and EVOO, were able to induce methylation changes in several PWBCs genes. These changes may have potential benefits in health; especially those changes in genes related to intermediate metabolism, diabetes, inflammation and signal transduction, which may contribute to explain the role of MedDiet and fat quality on health outcomes.
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Associations between genes in the one-carbon metabolism pathway and advanced colorectal adenoma risk in individuals with low folate intake.
Han, SS, Sue, LY, Berndt, SI, Selhub, J, Burdette, LA, Rosenberg, PS, Ziegler, RG
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2012;21(3):417-27
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Plain language summary
Colorectal cancer is the third most common cancer and third leading cause of cancer-related death in the US. Folate is essential for one-carbon metabolism, a pathway required by DNA synthesis, methylation, and repair. The aim of this study was to investigate associations between the risk of colorectal cancer and genes involved in one-carbon metabolism. Scientists looked at the folate intake, folate levels and genes of 500 people with advanced colorectal adenomas (benign tumours that have a high risk of becoming cancerous), and compared them to 500 healthy controls. Estimates of folate intake were based on a food frequency questionnaire which was completed by participants at the baseline of the study. Blood folate levels were also measured. People with the lowest intake of folate in their diets (0 to 262 micrograms/day) were at a 46% increased risk of advanced colorectal adenoma compared to people with the highest intakes (more than 466 micrograms/day). For those with the lowest intakes only, variations in several genes including adenosine deaminase (ADA) and cysteine dioxygenase (CDO1) were associated with adenoma risk. There were no associations between gene variations and adenoma risk in people with higher intakes of folate. The authors concluded that folate intake may interact with variations in one-carbon metabolism genes to modify colorectal adenoma risk.
Abstract
BACKGROUND Folate is essential for one-carbon metabolism, a pathway required by DNA synthesis, methylation, and repair. Low dietary and circulating folate and polymorphic variation in this pathway are associated with increased risk of colorectal adenoma and cancer. METHODS We genotyped 882 single nucleotide polymorphisms (SNP) in 82 one-carbon metabolism genes for 1,331 cases of advanced colorectal adenoma, identified by sigmoidoscopy at baseline, and 1,501 controls from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO). We evaluated associations between one-carbon genes and adenoma risk in all subjects and stratified by folate intake. We applied the Adaptive Rank Truncated Product (ARTP) method to assess statistical significance at the gene and pathway levels. RESULTS Folate intake was inversely associated with advanced colorectal adenoma risk [odds ratio (OR) by quartile = 0.85, P = 1.9 × 10(-5)]. We found no statistically significant associations between one-carbon genes and adenoma risk in all subjects. As hypothesized, we observed a statistically significant pathway-level association (P = 0.038) in the lowest quartile of folate; no significant associations were found in higher quartiles. Several genes including adenosine deaminase (ADA) and cysteine dioxygenase (CDO1) contributed to this signal (gene-level P = 0.001 and 0.0073, respectively). The most statistically significant SNP was rs244072 in ADA (P = 2.37 × 10(-5)). CONCLUSIONS AND IMPACT Stratification by dietary folate and application of the ARTP method revealed statistically significant pathway- and gene-level associations between one-carbon metabolism genes and risk of advanced colorectal adenoma, which were not apparent in analysis of the entire population. Folate intake may interact with associations between common variants in one-carbon metabolism genes and colorectal adenoma risk.