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Scientists Identify Gene Behind Inflammatory Bowel Diseases in Kids

by Rajashri on Sep 5 2008 1:47 PM

Scientists have identified a gene, called tumor necrosis factor receptor superfamily member 6B (TNFRSF6B) that influences whether children get diseases like Crohn's disease early in life.

The findings of the study by an international team also points to a potential new target for treatment.

Co-first author of the study, Subra Kugathasan, MD, said that while scientists have earlier found several genes that influence susceptibility to the two diseases, this is the first to focus on inflammatory bowel disease (IBD) with childhood onset.

Kugathasan's future research will focus on discovery of additional IBD genes and in depth study of how these genes influence disease onset and progression.

"Our novel candidate gene is in the same inflammatory pathway as some other susceptibility genes, so it may represent an accessible target for treatment," Nature quoted Kugathasan, as saying.

Kugathasan said that both genetics and the environment have an effect on the risk of getting inflammatory bowel disease. If one identical twin suffers from Crohn's disease, the other has a 60 percent probability of getting it too.

However, he noted that the incidence of disease has drastically increased over the last half century. He also suggested a key role of the environment in disease development. Smoking is an environmental factor that is particular strong in increasing the risk of Crohn's disease.

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"We have to conclude that the interactions between genetics and environment are responsible for most cases," he said.

The study compared the DNA of more than 1,000 children diagnosed with inflammatory bowel diseases at the average age of 11 with 4,250 controls (disease-free children), and confirmed the findings in a larger set of patients established by the British Wellcome Trust Case Control Consortium.

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They used gene chip microarray technology to scan thousands of one-letter alternative genetic "spellings" -- known to geneticists as single nucleotide polymorphisms (SNPs)-- spread throughout the patients' DNA.

Most of the SNPs made little difference when it came to affecting the risk of inflammatory bowel disease, but a few stood out, and two had not been seen before.

One new SNP led the scientists to TNFRSF6B, whose activity they found was associated with the degree of inflammation in the colon. The function of the second SNP is still under investigation.

TNFRSF6B encodes a protein that lengthens the duration of an immune response by regulating the longevity of activated white blood cells.

Kugathasan said that a related protein, tumor necrosis factor alpha, is the target of an existing antibody treatment for inflammatory bowel disease. This suggests that antibodies to TNFRSF6B could also be helpful in controlling the disease, he says.

The study was published online by the journal Nature Genetics.

Source-ANI
RAS/M


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