Study reveals genetic clues to chronic liver disease
18 March 2011
The disease affects approximately 35 out of every 100 000 adults and has no proven treatments. It causes irritation and swelling of the liver. The swelling blocks the liver's bile ducts, preventing the flow of bile - which is needed for the digestion of lipids. These obstructions damage liver cells, causing irreparable scarring.
Although it is known that primary biliary cirrhosis is an autoimmune disease, its underlying biological causes are not well understood. The new research involved every NHS Trust in the UK and compared the genomes of 2500 people with the disease with those from over 7500 healthy people.
The comparisons revealed 22 regions of the genome that differed significantly, 15 of which had not previously been identified. Many of these contained genes involved in regulating the immune system. One of these regulatory systems, known as the NF-κB pathway, had not previously been associated with primary biliary cirrhosis but is known to have a role in other autoimmune diseases, such as rheumatoid arthritis and multiple sclerosis.
"By scrutinizing the genes within these regions we were able to identify biological pathways that appear to underpin the disease, thus prioritising these for future research and highlighting their potential for therapeutic intervention," said Dr Carl Anderson, from the Wellcome Trust Sanger Institute, one of the senior authors on the paper.
The Wellcome Trust Case Control Consortium 3 (WTCCC3) uses genome-wide association studies to understand the genetics of several different diseases including primary biliary cirrhosis, anorexia nervosa and pre-eclampsia.
Image: A surgical team performing a liver transplant operation. Credit: Wellcome Images.
Reference
Mells GF et al Genome-wide association study identifies 12 new susceptibility loci for primary biliary cirrhosis. Nat Genet 2011 [epub ahead of print]
