To identify additional genes that are associated with IBD, the international team of researchers scanned the genome--all 22,000 or so genes--by testing more than 300,000 single nucleotide polymorphisms, or SNPs, in people with Crohn's disease. They looked for the presence of these SNPs in a similar number of people without IBD for comparison.
Out of the hundreds of thousands of SNPs, the genome-wide scan found three that were most strongly associated with Crohn's disease. Of those, two were in the CARD15 gene. However, the third SNP was in a different gene on a different chromosome.
When the researchers looked at the specific gene where the third SNP resided, they found that it coded for a protein that is part of the immune cell receptor for interleukin-23 (IL-23), an important mediator of inflammation in the body. However, when they began looking for all of the polymorphisms in the IL-23 receptor gene of affected individuals to determine which ones were the most detrimental, they made an unexpected discovery.
Although several polymorphisms were associated with a significantly increased risk of developing IBD, one appeared to confer a very strong protection against IBD.
"Of all the SNPs we studied in people with and without IBD, this protective SNP was the most statistically significant finding in our study. So, it took us a bit by surprise," said first author, Richard H. Duerr, M.D., associate professor of medicine and human genetics at the University of Pittsburgh. "What it means in terms of improving treatments for IBD patients, we are not sure yet. But, we speculate that it may be possible to mimic the conditions within the IL-23 inflammatory pathway that result from the chain of events initiated by this particular genetic variant."
Members of the consortium are attemp
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26-Oct-2006