An international team of researchers has identified
another gene mutation linked to the inflammatory bowel
diseases Crohn's disease and ulcerative colitis.
The team, including Johns Hopkins gastroenterologists
and geneticists, says the novel mutation is in the
interleukin-23 gene receptor present in healthy people
without Crohn's disease but rare in those with the
disease.
IL-23 is a protein that regulates chronic inflammation
and helps the body fight bacterial infections. Its
receptor, IL23R, is present on lymphocytes and macrophages,
white blood cells responsible for mounting immune response
to infections. IL-23 has long been linked to inflammatory
bowel diseases and autoimmune psoriasis, but this new
genetic variation in the protein's receptor offers a novel
pathway for tracking the disease process and for potential
drug treatments.
Results of the study, by a consortium of researchers
from Johns Hopkins and six other American and Canadian
institutions, appeared in Science Express, an online
publication of the journal Science, on Oct. 26.
"The IL-23 receptor variation we discovered appears to
affect the IL-23 pathway, altering the body's response to
chronic inflammation, which may trigger autoimmune
disease," said study co-author Steven R. Brant, associate
professor of
medicine and director of research and the genetics
laboratories of Hopkins' Harvey M. and Lyn P. Meyerhoff
Inflammatory Bowel Disease Center. "The fact that this gene
has already been implicated in another autoimmune disease
like psoriasis offers strong evidence that we are on the
right track.
In the Crohn's study, researchers located the IL23R
disease-associated protein variant by scanning nearly all
the 22,000 genes that make up the human genome. The study
looked at 547 test subjects with Crohn's disease and 548
healthy controls. Patients were recruited from six of the
seven centers in the consortium. Researchers examined more
than 300,000 variations in the genetic code, known as
single nucleotide polymorphisms, or SNPs, to identify which
of the variations among these 22,000 genes can explain the
genetic predisposition to developing Crohn's disease. SNPs
are commonly occurring variations in DNA code that are
routinely used as a method for finding genetic links to
diseases. Researchers scanned the genomes using a
relatively new technology that allows researchers to study
variations found in nearly all human genes for association
with diseases.
Researchers found that test subjects with Crohn's
disease were roughly fourfold less likely to have an SNP
variation that alters an important amino acid of the IL-23
receptor gene.
More than 1 million Americans have Crohn's disease or
ulcerative colitis. Because inflammatory bowel disease
tends to run in families and is more prevalent in certain
ethnic populations, scientists have long suspected that
there is a significant genetic component. A previous study,
conducted in part at Johns Hopkins, identified another gene
mutation on the CARD15/NOD2 gene, common in people with
Crohn's disease, but Brant said the new gene is a better
candidate for drug treatments.
"IL-23 is directly linked to an inflammatory pathway,
making it a better candidate for drug therapies than
CARD15/NOD2," he said.
Brant said the team has identified additional gene
variations potentially related to Crohn's disease, and the
consortium will investigate these as well.
Co-author Themistocles Dassopoulos, an assistant
professor of medicine at the Meyerhoff Inflammatory Bowel
Disease Center, said, "As more genes associated with
Crohn's disease are discovered, we envision a time when
gene testing may provide important guidance regarding the
prognosis and treatment of each patient."
The study was funded by the National Institute of
Diabetes and Digestive and Kidney Diseases.
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