Scientists demonstrate how genetic variations cause eczema

New research supported by the National Institutes of Health describes how two relatively common variations in a gene are named KIF3A are responsible for a limited skin barrier that allows increased water loss of the skin, and promotes the development of atopic dermatitis, commonly known as eczema. This finding could lead to genetic tests that support parents and physicians to take steps to protect potentially vulnerable children from developing atopic dermatitis and additional allergic diseases.

Atopic dermatitis is an inflammatory skin condition that affects up to 20% of children in developed countries. This chronic disease is characterized by dry, thickened and intensely itchy skin, especially in skin folds. People with eczema are more susceptible to infections from bacteria, viruses and fungi and often develop additional allergic diseases such as asthma.

KIF3A is a gene that encodes a protein involved in generating signals from the outside to the inside of a cell, part of a complex sensory apparatus. Earlier, scientists had identified an association between two genetic variations in KIF3A and asthma in children who also had eczema. In the new study, the researchers found that these variations, as single nucleotide polymorphisms (SNPs), share the KIF3A gene to a form that can regulate, through a process called methylation, the rate at which a gene is transcribed into the blueprint for protein production. The researchers confirmed that skin and nasal lining cells of people with the KIF3A SNP variants had more methylation and contained less blueprints for the KIF3A protein than cells containing KIF3A miss the SNPs. In addition, the researchers demonstrated that people with the SNP-created regulatory sites had higher levels of water loss from the skin.

To determine whether lower levels of KIF3A cause atopic dermatitis, the researchers studied mice that lacked the mouse version of KIF3A in skin cells. They found that these mice also had increased water loss from the skin due to a dysfunctional skin barrier and were more likely to develop features of atopic dermatitis. The researchers concluded that the presence of one or both of the two SNPs in humans KIF3A leads to lower production of the KIF3A protein, promoting dysfunction of the barrier that normally keeps skin well hydrated, thereby increasing the chance that a person will develop atopic dermatitis.

Now researchers have determined that these KIF3A SNPs increase the risk of atopic dermatitis, beginners could potentially be screened for them. Therapies specifically targeted at skin water loss, such as intensive topical moisturizers, could be evaluated for their ability to prevent atopic dermatitis in children with the SNPs. The occurrence of atopic dermatitis in early childhood could in turn prevent a cascade of additional allergic diseases later in life, such as asthma, food allergies and allergic rhinitis – a cascade called the atopic march.

This research was co-funded by the National Institute of Allergy and Infectious Diseases and the National Center for Advancing Translational Sciences, both part of NIH. The study was led by Gurjit K. Khurana Hershey, MD, Ph.D., Professor of Pediatrics and Director of the Department of Asthma Research at Cincinnati Children’s Hospital Medical Center, which is part of the NIAID Support Asthma and Allergic Diseases Cooperative Research Centers.