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The Link Between Methylation and Disease

Methylation is a relatively simple process that underlies many of our bodies’ most complex functions. According to the National Cancer Institute, it is “a chemical reaction in the body in which a small molecule called a methyl group gets added to DNA, proteins, or other molecules. The addition of methyl groups can affect how some molecules act in the body.”

When it comes to DNA, methylation specifically impacts gene expression. It doesn’t alter DNA, but it can, for instance, turn a gene on or off. While methylation plays a role in fundamental processes from embryonic development to metabolism, research shows that abnormal methylation may lie at the root of many of our most common chronic diseases. Some study highlights:


Methylation and Heart Disease

A 2015 review of research published in Drug Discovery Today examined the link between epigenetic mechanisms—including DNA methylation—on fetal heart development, as well as the role aberrant epigenetic regulation plays in the development of heart disease. The researchers noted that recent studies on mice had shown that heart development was associated with greater increases than decreases in DNA methylation of cardiac-specific genes, although methylation’s exact role in fetal heart development is still poorly understood. “The role of DNA methylation in heart development probably varies by genomic location within cells, by cell type within the developing heart, as well as across various stages of development,” the researchers wrote. “Further work is needed to elucidate the role of DNA methylation in the regulation of heart development.”

When it comes to the development of heart disease, the review found evidence that abnormal DNA methylation has been implicated in hypertension, cardiomyopathies, atherosclerosis, and coronary artery disease. The researchers noted that a DNA methylation inhibitor (5-azaC) had generated some interest as a therapeutic agent, but that “the potential benefits of 5-azaC in cardiac regeneration studies are limited by toxicity, including myeloid suppression and induction of cardiomyocyte cell death.”


Methylation and Cancer

A 2016 review published in Advances in Experiment Medicine and Biology set out to explore the genetic and epigenetic changes that drive the malignant transformation of cancer cells, noting that “With the advent of next-generation sequencing and large-scale multinational consortium studies, it has become possible to profile the genomes and epigenomes of thousands of primary tumors from nearly every cancer type. From these genome-wide studies, it became clear that the dynamic regulation of DNA methylation is a critical epigenetic mechanism of cancer initiation, maintenance, and progression.”

Research cited in the review has shown that because DNA methylation can regulate gene expression, it can affect cell growth, proliferation, and repair, meaning that abnormal methylation can cause tumor growth and proliferation. But the good news, the researchers wrote, is that “unlike genetic changes, DNA methylation alterations can be potentially reversed with the help of methylation inhibitors. This can achieve therapeutic effects by reactivating silenced tumor suppressor genes, downregulating overexpressed oncogenes, and stimulating immune response toward cancer cells.”


Methylation and Diabetes

Heart disease and cancer aren’t the only diseases affected by abnormal DNA methylation. This basic biochemical process has also been implicated in the development of diabetes. A 2017 review, published in Pediatric Diabetes found that “alterations in DNA methylation may contribute to the increased prevalence of both Type 1 and Type 2 diabetes.”

The review examined the existing research into the link between DNA methylation, gene expression, and the development of diabetes and related complications. While noting that “[t]he use of genome wide DNA methylation profiles as a biomarker to predict at-risk patients is in its infancy and needs additional study,” the authors concluded that “[d]eveloping a model incorporating genetic and DNA methylation changes together could be useful for development of effective diagnostic approaches and innovative therapeutic targets for diabetes.”



These reviews are just the tip of the iceberg of the research linking abnormal DNA methylation with chronic disease. Studies have implicated methylation in the development of a host of other conditions, including osteoporosis and osteoarthritis, autoimmune issues, and Parkinson’s disease. And a study published in the Annual Review of Pharmacology and Toxicology found that “The most widespread of senile dementias, Alzheimer’s disease, is associated with altered DNA methylation in both laboratory animal models and human postmortem brain tissue.”

The reasons why DNA methylation becomes altered or abnormal are varied and include genetic variations, exposure to environmental toxins, and lifestyle factors such as smoking, alcohol abuse, and nutrient deficiencies, the latter being the most easily corrected. Because they are vital contributors to the methylation process, adequate intake of B vitamins may help prevent abnormal DNA methylation. Studies have found that B-vitamin supplementation can result in DNA methylation changes and may help reduce the risk of disease, including cancer. While more research is needed, the link between B vitamins and healthy methylation has strong implications for the future of disease prevention.



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