Primary Sclerosing Cholangitis Is A Unique Condition
April 22, 2013

Genetic Research Proves Autoimmune Liver Disease Is A Unique Condition

redOrbit Staff & Wire Reports - Your Universe Online

Using DNA genotyping technology, researchers from the Wellcome Trust Sanger Institute have determined that primary sclerosing cholangitis (PSC), a rare autoimmune disease affecting the liver, is a unique condition and not a complication of inflammatory bowel disease (IBD).

“Before our study, it was never quite clear whether PSC was a complication of IBD or a distinct disease in its own right. We have proven it to be a unique disease, and hope that our results will inform the development of more effective treatments, designed to target the biological pathways involved in causing the disease,” lead author Dr. Carl Anderson said in a statement.

The study, an advanced copy of which was published on the Nature Genetics website Sunday, involved an international team of scientists who recruited patients from 13 countries throughout Europe and North America. Dr. Anderson and his colleagues reported discovering nine new genetic regions linked with PSC, which they describe as a chronic and progressive disease which funnels bile from the liver into the intestines. That brings the total number of genetic regions associated with the disease to 16, they said.

“The team used DNA genotyping technology to survey more thoroughly regions of the genome known to underlie other immune-related diseases to discover if they also play a role in PSC susceptibility,” the Wellcome Trust Sanger Institute explained. “In addition to the nine genetic regions newly associated, they also saw strong signals at three regions of the genome previously associated with the disease. Of these twelve genetic regions, six are also associated with IBD, while the six other regions showed little to no association in a recent large study of IBD.”

While PSC is genetically related to IBD, the new research proves that it is, in fact, a unique disease, the researchers said. Only half of the newly discovered genetic regions were shared with IBD, which also impacts roughly 70 percent of those who suffer from PSC. The condition itself can cause inflammation of the bile ducts and liver scarring which can lead to cirrhosis and liver failure. There are no effective treatments for PSC, and even though it affects just one out of every 10,000 people, it is one of the leading causes of liver transplant surgery.

“Using the Immunochip genotyping chip, we can pull apart the genetic relationships between these autoimmune diseases and begin to see not only their genetic similarities, but also the differences,” said first author Jimmy Liu, a PhD student at the UK-based research center. “As PSC is a rare disorder, sample collection is more difficult than for other, more common, autoimmune diseases. We hope that with more samples from patients, we'll be able to link more genetic regions to the disease, and it will become easier to identify underlying pathways that could act as therapeutic targets.”

According to Dr. Anderson´s team, three of the genetic regions associated with PSC fall within a single biological system which underlies variation in the immune system response cells known as T cells. One of them, HDAC7, has been proven to be a key factor in immune tolerance, and the new research suggests that exploring drugs which affect this genetic region could one day be used to treat the condition. The researchers now plan to continue their work by conducting a high-powered search throughout the entire genomes of PSC patients, looking for specific regions associated with the condition beyond those areas included on the Immunochip genotyping chip.