Singapore, Sept 2, 2008: Researchers have discovered two new genes that increase the risk of developing inflammatory bowel disease (IBD) in childhood. While further study is needed to identify the specific disease-causing mutations in these new genes, the researchers say the genes are particularly strong candidates to be added to the list of genes already known to affect IBD.

 

"As we continue to find genes that interact with each other and with environmental influences in this complex, chronic disease, we are building the foundation for personalized treatments tailored to a patient's genetic profile," said co-first author Dr Robert N. Baldassano, director of the Center for Pediatric Inflammatory Bowel Disease at The Children's Hospital of Philadelphia.

 

"We will resequence the gene regions we have identified to pinpoint the causative mutations in these genes. We strongly suspect one gene will provide a compelling target for drug development, given what's known about its biology," added study leader Dr Hakon Hakonarson, director of the Center for Applied Genomics at Children's Hospital.

 

Both authors direct research programs at Children's Hospital and are also faculty members of the University of Pennsylvania School of Medicine. Their study, performed in collaboration with researchers from the Medical College of Wisconsin, The University of Utah, Cincinnati Children's Hospital and two research hospitals in Italy, appeared in advance online publication August 31 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 gastrointestinal tract, and half have ulcerative colitis, which is limited to the large intestine.

 

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.