Scientists demonstrate how genetic variations cause eczema
Finding could lead to genetic tests that identify infants at risk for the disease

Date:
August 14, 2020
Source:
NIH/National Institute of Allergy and Infectious Diseases
Summary:
New research delineates how two relatively common variations in a
gene called KIF3A are responsible for an impaired skin barrier that
allows increased water loss from the skin, promoting the development
of atopic dermatitis, commonly known as eczema. This finding could
lead to genetic tests that empower parents and physicians to take
steps to potentially protect vulnerable infants from developing
atopic dermatitis and additional allergic diseases.



FULL STORY ==========================================================================
New research supported by the National Institutes of Health delineates how
two relatively common variations in a gene called KIF3A are responsible
for an impaired skin barrier that allows increased water loss from the
skin, promoting the development of atopic dermatitis, commonly known as
eczema. This finding could lead to genetic tests that empower parents
and physicians to take steps to potentially protect vulnerable infants
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, particularly
in skin folds. People with eczema are more susceptible to bacterial,
viral and fungal skin infections and frequently develop additional
allergic diseases such as asthma.

KIF3A is a gene that codes for a protein involved in generating signals
from the outside to the inside of a cell, part of a complex sensory
apparatus.

Previously, 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, or single nucleotide polymorphisms (SNPs), changed parts of 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 investigators confirmed that skin and nasal-lining cells from people with
the KIF3A SNP variants had more methylation and contained fewer blueprints
for the KIF3A protein than cells in which KIF3A lacked the SNPs. In
addition, the researchers demonstrated that people with the SNP-created regulating sites had higher levels of water loss from the skin.

To determine whether lower levels of KIF3A caused atopic dermatitis,
the scientists studied mice lacking 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 investigators concluded that
the presence of either or both of the two SNPs in human KIF3A leads
to lower production of the KIF3A protein, promoting dysfunction of the
barrier that normally keeps skin well hydrated, thereby increasing the likelihood that a person will develop atopic dermatitis.

Now that investigators have established that these KIF3A SNPs increase
the risk for atopic dermatitis, infants could potentially be screened
for them.

Therapies directed specifically at water loss from the skin, such as
intensive topical moisturization regimens, could be evaluated for their
ability to prevent atopic dermatitis in children with the SNPs. Preventing atopic dermatitis in early childhood could in turn prevent a cascade of additional allergic diseases later in life, such as asthma, food allergy
and allergic rhinitis -- a cascade known as 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, M.D., Ph.D., professor of pediatrics and director of the Division
of Asthma Research at Cincinnati Children's Hospital Medical Center,
which is part of the NIAID- supported Asthma and Allergic Diseases
Cooperative Research Centers.


========================================================================== Story Source: Materials provided by NIH/National_Institute_of_Allergy_and_Infectious Diseases. Note: Content
may be edited for style and length.


========================================================================== Journal Reference:
1. Mariana L. Stevens, Zhonghua Zhang, Elisabet Johansson, Samriddha
Ray,
Amrita Jagpal, Brandy P. Ruff, Arjun Kothari, Hua He, Lisa
J. Martin, Hong Ji, Kathryn Wikenheiser-Brokamp, Matthew
T. Weirauch, Dorothy M.

Supp, Jocelyn M. Biagini Myers, Gurjit K. Khurana Hershey. Disease-
associated KIF3A variants alter gene methylation and expression
impacting skin barrier and atopic dermatitis risk. Nature
Communications, 2020; 11 (1) DOI: 10.1038/s41467-020-17895-x ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/08/200814123202.htm

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