--Findings Linked to a Key Molecule Active in GI Inflammation--
PHILADELPHIA, Nov. 16 /PRNewswire-USNewswire/ -- In the largest, most
comprehensive genetic analysis of childhood-onset inflammatory bowel disease
(IBD), an international research team has identified five new gene regions,
including one involved in a biological pathway that helps drive the painful
inflammation of the digestive tract that characterizes the disease.
A research team led by Hakon Hakonarson, M.D., Ph.D., director of the Center
for Applied Genomics at The Children's Hospital of Philadelphia, says that the
findings advance the scientific understanding of how IBD develops. "This is an
evolving story of discovering what genes tell us about the disease," said
Robert N. Baldassano, M.D., a co-first author of the study and director of the
Center for Pediatric Inflammatory Body Disease at Children's Hospital.
"Pinpointing how specific genes act on biological pathways provides a basis
for ultimately personalizing medicine to an individual's genetic profile."
The study appears online today in Nature Genetics.
IBD is a painful, chronic inflammation of the gastrointestinal tract,
affecting about two million children and adults in the United States. Of that
number, about half suffer from Crohn's disease, which can affect any part of
the GI tract, and half have ulcerative colitis, which is limited to the large
intestine.
Most gene analyses of IBD have focused on adult-onset disease, but the Center
for Applied Genomics--one of the world's largest pediatric genotyping
programs--at Children's Hospital has concentrated on childhood-onset IBD,
which tends to be more severe than adult-onset disease. The researchers
performed a genome-wide association study on DNA from over 3,400 children and
adolescents with IBD, plus nearly 12,000 genetically matched control subjects,
all recruited through international collaborations in North America and
Europe.
In a genome-wide association study, automated genotyping tools scan the entire
human genome seeking gene variants that contribute to disease risk.
The study team identified five new gene regions that raise the risk of
early-onset IBD, on chromosomes 16, 22, 10, 2 and 19. The most significant
finding was at chromosome locus 16p11, which contains the IL27 gene that
carries the code for a cytokine, or signaling protein, also called IL27. "This
cytokine acts on a biological pathway, the T-helper 17 pathway, which plays a
key role in causing intestinal inflammation," said Hakonarson. T helper 17
cells are recently discovered cells that lead to severe inflammation and
tissue injury in autoimmune diseases. IBD is an autoimmune disease, in which a
person's immune system runs out of control and attacks the body.
"There are many cytokines in our immune system, but our research strongly
suggests that IL27 has a primary causative role in IBD," added Hakonarson.
"This gene discovery makes sense in terms of our functional understanding of
the disease."
Some current IBD drugs are monoclonal antibodies that act on another cytokine,
called tumor necrosis factor, which contributes to inflammation. Although much
research remains to be done, the current study may provide a basis for
developing drugs that target the cytokine IL27's action, for patients with the
disease-causing IL27 gene variant.
One strength of the current study, in addition to its large sample size, is
the collaboration of many leading pediatric IBD research programs. In addition
to The Children's Hospital of Philadelphia, other centers with principal
investigators who played key roles were the Hospital for Sick Children of the
University of Toronto; the University of Edinburgh, UK; Cedars Sinai Medical
Center, Los Angeles; Emory University, Atlanta; and the IRCCS-CSS Hospital, S.
Giovanni Rotondo, Italy.
The Children's Hospital of Philadelphia supported this research, along with
the Primary Children's Medical Center Foundation and grants from the National
Center for Research Resources, a member of the National Institutes of Health.
The researchers used data provided by the International HapMap Consortium and
the Wellcome Trust Case Control Consortium.
"Common variants at five new loci associated with early-onset inflammatory
bowel disease," Nature Genetics, published online Nov. 15, 2009
http://dx.doi.org/10.1038/ng.489
About The Children's Hospital of Philadelphia: The Children's Hospital of
Philadelphia was founded in 1855 as the nation's first pediatric hospital.
Through its long-standing commitment to providing exceptional patient care,
training new generations of pediatric healthcare professionals and pioneering
major research initiatives, Children's Hospital has fostered many discoveries
that have benefited children worldwide. Its pediatric research program is
among the largest in the country, ranking second in National Institutes of
Health funding. In addition, its unique family-centered care and public
service programs have brought the 441-bed hospital recognition as a leading
advocate for children and adolescents. For more information, visit
http://www.chop.edu.
Contact: John Ascenzi
The Children's Hospital of Philadelphia
Phone: (267) 426-6055
Ascenzi@email.chop.edu
SOURCE The Children's Hospital of Philadelphia
John Ascenzi, The Children's Hospital of Philadelphia, +1-267-426-6055,
Ascenzi@email.chop.edu
