April 14, 2009 — Scientists of the Max
Delbrück Center for Molecular Medicine (MDC) Berlin-Buch and Charité –
University Medical School, Berlin, Germany, in collaboration with
researchers from the Klinikum rechts der Isar of Technical University
Munich and Christian Albrecht University, Kiel, have identified a gene
variant on chromosome 11 that is associated with an increased risk of
In a large genome-wide association study the researchers scanned the
genomes of more than 9600 participants from Germany, Poland and the
Czech Republic. "Our findings cast new light on the pathogenesis of the
disease," said Professor Young-Ae Lee (Charité / MDC). The
pediatrician-researcher and her collaborators hope the study will lead
to a new approach to targeted therapy for this chronic skin disorder.
More and more people suffer from atopic dermatitis, which is also
known as atopic or infantile eczema. Atopic dermatitis is a chronic
(long-lasting) inflammatory skin disease that typically affects the
large flexures such as the bend of the elbows or the back of the knees.
Patients suffer from recurrent flares of intense itching, dryness and
redness of the skin, with weeping of clear fluid in the acute stage,
and skin thickening (lichenification) in the chronic stage. Along with
hay fever and asthma, atopic dermatitis is one of the most common
allergic disorders. In the industrialized countries about 15 percent of
young children are affected.
Atopic dermatitis is typically the first clinical manifestation of
allergic disease. In most cases atopic dermatitis appears within the
first few years of life. For the majority of affected children this
marks the beginning of an "allergic career", which in later years
evolves into hay fever or asthma. Just what triggers the outbreak of
atopic dermatitis is not yet fully understood. However, epidemiological
studies indicate that the genetic contribution is substantial.
For that reason, of the total of 9600 study participants, the
scientists decided to scrutinize the genomes of 3011 individuals more
closely. These included children and adults with atopic dermatitis,
healthy controls, as well as entire families in which at least two
children have atopic dermatitis. The researchers scanned the entire
genome, searching for genetic variants that are especially common in
atopic dermatitis patients.
The study demonstrates that several genes are involved in the
pathogenesis of atopic dermatitis. Most importantly, the researchers
identified a variant on chromosome 11 that is particularly common in
the patients with atopic dermatitis. This variant is located in a
region containing the gene C11orf30 which encodes the protein EMSY. The
scientists suspect that a mutation in this gene is associated with
atopic dermatitis. However, the exact role of EMSY in atopic dermatitis
still needs to be investigated.
Same variant also a risk factor for Crohn’s disease
The same variant on chromosome 11 is also common in patients with
Crohn’s disease, a chronic inflammatory disease of the gastrointestinal
tract. Scientists therefore suspect that this variant on chromosome 11
will unravel a novel common disease mechanism that can lead to chronic
inflammation of various organs. The variant is very widespread: in
Europe, 36 percent of the population are carriers. Now the MDC and
Charité scientists want to decipher the exact function of EMSY in
Furthermore, the scientists show that other previously unknown
variants in genes related to the outermost skin layer (epidermis)
increase the risk for the disease. The researchers hope that their
findings will contribute to improved treatment for atopic dermatitis
sufferers. "To develop a targeted intervention," they explained, "we
must first fully understand the underlying disease mechanism."