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Genetics defines a distinct liver disease
Date:4/21/2013

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.

"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," says Jimmy Liu, PhD student and first author from the Wellcome Trust Sanger Institute. "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."

Three of the genetic regions associated with PSC fall within a single biological system that underlies variation in T cells, cells important to our immune response. One gene that controls this pathway, HDAC7, is known to be a key factor in immune tolerance and the new data strongly suggests exploring the possibility that drugs affecting HDAC7 function may serve as future therapeutics in PSC.

In an extended analysis, the team identified an additional 33 genetic regions that are also involved in several common immune-mediated conditions (celiac disease, Crohn's disease, ulcerative colitis, type 1 diabetes, rheumatoid arthritis, sarcoidosis and psoriasis). This analysis shows that PSC shares many genetic risk loci with other immune-mediated diseases and opens up the possibility for testing drugs known to be effective in genetically similar diseases for efficacy in PSC.

The next step for the team is to do a high-powered search throughout the entire genomes of PSC patients to find specific regions associated with PSC outside of the regions included on the Immunochip genotyping chip.

"This study has uncovered more about the gene
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Contact: Aileen Sheehy
press.office@sanger.ac.uk
44-012-234-96928
Wellcome Trust Sanger Institute
Source:Eurekalert

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