Gene Variants Increase Risk for Dysfunctional Skin Barrier, Asthma, and Food Allergies

Published August 2020 | Nature Communications

In the fight against allergens, skin is the first barrier. When this barrier is dysfunctional, environmental exposures can more easily reach other tissues, raising the risk of developing asthma and food allergies.

What controls skin barrier function? By integrating data from human and mouse studies, a research team led by first author Mariana Stevens and senior corresponding author Gurjit Khurana Hershey, MD, PhD, found that two common variants in the KIF3A gene play a major role. In young children, these variants increase the risk of having a dysfunctional skin barrier and developing atopic dermatitis, also known as eczema, which affects up to 20 percent of all children.

Although eczema usually resolves as children age, many go on to develop more severe conditions including asthma and food allergies. Understanding the genetic mechanisms of eczema could make it easier to identify which of these children are most likely to develop other allergic conditions.

While previous studies have shown that malfunctioning KIF3A in lung and gut tissues leads to asthma and food allergies, this study is the first to connect these allergy risks to a damaged skin barrier.

“This study adds evidence to a rising theory that skin health is more closely connected to lung and gut health than many have suspected,” Hershey says. “KIF3A is a new target for therapies to prevent and treat eczema and allergic diseases.”

Next, the research team aims to develop a rapid screening test and search for drug compounds that might someday be useful in restoring the disrupted functions of the KIF3A gene.

A Tale of Two SNPs

Allergic disease-associated KIF3A SNPs create new CpG sites, which are highly methylated in individuals carrying the alternate allele leading to decreased KIF3A expression. Decreased KIF3A results in increased TEWL due to defective cell-cell adhesion, and increased susceptibility to the development of atopic dermatitis. ALRG = allergen.