Epigenetics in Atopic Dermatitis - Is It Inherited?
Atopic eczema, also known as atopic dermatitis, is a chronic inflammatory skin condition. Patients with eczema have intense itching that leads to frequent scratching and sleep disturbances. Most cases present in early childhood and currently affects 10-20% of children and over 10% of adults in the United States.[1,2] Eczema is associated with atopy, the term used to describe the tendency for individuals to develop allergic conditions like asthma, food allergies, and seasonal allergies due to their extremely sensitive immune response to common allergens. The cause of eczema is complex and depends on the genes inherited from parents and the environment, which includes allergens, irritants, pollutants, and infections.
What Is Epigenetics?
DNA is the building block that contains our hereditary material, or our genetics. Historically, scientists thought that the sequence of our DNA is what determines who we are. However, recent researchers have found that our body actually modifies the expression of our DNA. There are 3 major ways our bodies do this: methylation, chromatin modification, and noncoding RNAs. Methylation is the process of chemically modifying the DNA after the DNA has been copied. Methylation typically turns genes off and demethylation, removing the methylation, turns genes on. Chromatin is the large package that contains the DNA in each and every cell in the body. Chromatin modification makes the package easier or harder to open, making DNA more or less accessible. Noncoding RNAs are small pieces of DNA that can cover up and hide parts of DNA to turn genes off or make genes more visible, turning them on. These changes in DNA expression are collectively called epigenetics. The exact reasons that influence when and which genes get turned on or off is not known; however, both external environmental factors and our intrinsic genetic programming can play a role in epigenetics.
Researchers have found that factors that lead to eczema may, in fact, begin before birth. A subset of immune cells called regulatory T cells (Tregs) plays an essential role in the development of allergy. Children with low levels of Tregs are at greater risk of developing allergic diseases. Certain factors during pregnancy affect the DNA methylation of a gene important for Treg production, causing low Treg levels in the baby. These factors include cigarette smoke, the mother’s allergies, and whether there are signs of inflammation in the mother’s blood. According to a study by Liang et al., these factors increase the risk that the mother’s child will develop eczema. Exposure to tobacco, while a woman is pregnant, has also been associated with a high level of a specific noncoding RNA which is known to cause low numbers of Tregs. This increases the risk that the baby will develop eczema or other allergic diseases before 3 years of age. An additional study found that children with high prenatal tobacco smoke exposure and children who are diagnosed with eczema at age 2 both have lower levels of DNA methylation of a gene called thymic stromal lymphopoietin (TSLP). TSLP is involved in both asthma and eczema and methylation turns on TSLP gene expression.
Up to one-third of children with eczema have food allergies or sensitivities, so it is reasonable to assume that nutrition affects eczema through epigenetics. A major gene important in DNA methylation is the DNMT1 gene. In patients with atopic eczema, DNMT1 expression is lower in their immune cells, so they have less methylation overall. Interestingly, genistein, a polyphenol found in soybeans, and selenium have been found to decrease levels of DNMT1 in various cell types. Folate, choline, and vitamin B12 can also directly affect DNA methylation. They affect DNA expression through methylation of certain genes. In eczema, there have been multiple studies showing mixed results with these vitamins. In a study with mice, a diet high in folate, choline, and vitamin B12 was associated with an increased risk of developing eczema. Another study showed that prenatal supplementation with folate, choline, and vitamin B12 increased the risk that the baby would develop atopy. They found that these supplements increased the methylation of a different gene known to prevent atopic diseases like asthma and eczema. This means the supplements turned off a gene that prevents eczema from developing, leading to an increased risk for eczema. Other studies have been mixed on these results, but it is fair to say that nutrition does affect epigenetics leading to different outcomes in eczema.
Sometimes Bacteria Are the Good Guys
Bacteria are everywhere, including all over and throughout the body. As it turns out, the types and sheer number of bacteria on individuals may impact the way the body’s immune system functions. After birth, a child is exposed to many bacteria. Once these bacteria take up residence on the baby, DNA modification occurs which stimulates the immune system to function. In one study with mice, bacteria introduced prenatally caused modification of chromatin, the package that contains DNA within cells to change the balance of the immune system, decreasing the likelihood of developing eczema. Human studies have shown that alterations in the types of bacteria are associated with allergic diseases. Infants treated with antibiotics early in life, changing the natural bacterial colonies, were shown to have an increased risk of developing allergic diseases. Even studies on the prenatal effects of bacteria in the environment have been conducted. One study showed that a harmless bacterium, named Acinetobacter lwoffii, in rural farming environments provided protection from allergic disease by increasing the number of Tregs. This increase in Tregs was accomplished through the decreased DNA methylation of a gene important for Treg production. It appears that certain bacteria may have positive influences on immune function and decrease the risk of developing allergic disease.
Researchers continue to uncover additional epigenetic mechanisms important in the development of atopic eczema. These mechanisms are ways that our DNA gets modified in our body. Epigenetics is the missing link between disease and the surrounding environment. There are still many more pathways to uncover in eczema, providing further ways to relate these effects to our environment.
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