childhood tends to be more severe than adult-onset
disease, and is more likely to affect the colon than other areas of the GI
tract. Those age-related differences in IBD spurred the current research
team to do their gene hunting in childhood-onset disease. "Although the
gene variants we found may have a stronger signal in pediatric IBD than in
adult- onset IBD, we do not believe them to be limited to varieties of the
disease that begin in childhood," said Baldassano.
The researchers performed a genome-wide association study, searching
for genetic variations in DNA samples from 1,000 patients with
childhood-onset IBD, compared to samples from 4,250 healthy subjects. Both
patients and controls were of European ancestry.
In addition to finding gene variations previously reported by other
groups, the study team identified two novel gene variants, one on
chromosome 20 and the other on chromosome 21. They then replicated their
findings with studies using additional samples from other sources.
The researchers say that the TNFRSF6B gene on chromosome 20 is a
compelling candidate, because it is already known to participate in the
biological pathway of a protein called tumor necrosis factor (TNF). TNF is
a cytokine, a chemical messenger that plays a key role in the harmful
inflammation characteristic of IBD.
Some current treatments for IBD use monoclonal antibodies that
selectively bind to a type of TNF involved in the disease (Among those
drugs are infliximab, adalimumab and certolizumab). "As we better
understand the complex gene interactions in IBD, we may be able to diagnose
patients by their genetic profile to predict who will better respond to
anti-TNF drugs," said Hakonarson. Anti-TNF medications such as those
mentioned above are currently given intravenously or as injections, said
Baldassano, who added, "If better knowledge of the disease pathway enables
pharmaceutical companies to develop anti-TNF drugs in pill form, the
medications will b
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SOURCE Children's Hospital of Philadelphia Copyright©2008 PR Newswire. All rights reserved | |
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