Researchers have identified 15 genetic regions that provide clues into the risks of developing primary biliary cirrhosis

New Clues For Chronic Liver Cirrhosis

(Ivanhoe Newswire) -- Researchers have identified 15 genetic regions that provide clues into the risks of developing primary biliary cirrhosis (PBS), an autoimmune disease of the liver that affects nearly 95 out of every 100,000 women over 45 in the U.S. and U.K. every year.

PBS is marked by the slow progressive destruction of the small bile ducts within the liver. When these ducts are damaged, bile builds up in the liver and over time damages the tissue. This can lead to scarring, fibrosis and cirrhosis.

Based on the genomes of 2,500 patients with PBS and more than 7,500 healthy people, researchers aim to unravel the role of genetic variation in numerous human diseases. The study suggests that several key immune processes underlie susceptibility to PBS.

"To gain an insight into the causes of primary biliary cirrhosis we compared genetic data from patients and healthy volunteers and found 22 regions of the genome that differed significantly, 15 of which had not previously been identified," which Dr. Carl Anderson, from the Wellcome Trust Sanger Institute and one of the senior authors on the paper, was quoted as saying.

"By scrutinizing the genes within these regions we were able to identify biological pathways that appear to underpin the disease, thus prioritizing these for future research and highlighting their potential for therapeutic intervention."

"This study is a key first step in our efforts to unravel the biological complexity of primary biliary cirrhosis and further research building on these results is already underway."

Researchers discovered that several of the 15 novel regions contain genes involved in regulation of the immune system, with three immune pathways particularly prominent. One in particular, the NF-?B pathway, had not been associated with PBS in the past although it had been implicated in other autoimmune and inflammatory diseases such as rheumatoid arthritis, multiple sclerosis in addition to asthma. All in all, five of the identified genomic regions are thought to play a role in this pathway and further work is being planned to clarify how genetic mutations apparent in these regions cause PBS as well as other related diseases.

"For clinicians involved in the management of primary biliary cirrhosis, this study is exciting because it provides new and meaningful insight into the biological origins of this condition," which Dr. George Mells, from the Academic Department of Medical Genetics at the University of Cambridge and a first author on the study, was quoted as saying.

"This will undoubtedly inform the development of more effective treatments, designed to target the biological pathways involved in causing the disease. The study is also a triumph of collaboration. Every NHS Trust in the UK was involved in recruitment of patients and the patient community itself was mobilized by efforts from the PBC Foundation.”

"By working together, we have recruited almost one in six primary biliary cirrhosis patients in the UK; completed the largest genome-wide association study of primary biliary cirrhosis to date and established a research consortium that will form the foundation of further clinical, genetic and therapeutic studies."

Of the 22 regions identified in this study of PBS, 12 have been formerly associated with other autoimmune disorders such as type-1 diabetes, multiple sclerosis and psoriasis. Working out how these shared pathways interact with those that, at this moment in time, appear to be unique to primary biliary cirrhosis is probable to lead to vital therapeutic breakthroughs.

"The publication of this paper is no routine academic matter for people with primary biliary cirrhosis," which Collette Thain, MBE, Chief Executive of the PBC Foundation, was quoted as saying. "For us, it means hope – one step towards understanding how best to treat and cure. It is a testament to the perseverance and ingenuity of all the scientists who worked on this project. But because this was a collaborative project, part funded by the PBC Foundation and directly involving patients, it is also an example of how people with conditions like primary biliary cirrhosis can work together with scientists and physicians to find solutions.”

"As a sufferer myself, it is hard to put into words what an exciting breakthrough like this means to me and all the other people with primary biliary cirrhosis. Research like this brings a brighter tomorrow ever closer."

SOURCE: Wellcome Trust Case Control Consortium 3 (WTCCC3), March 13, 2011