A team of scientists has used a new technology to uncover three genetic regions associated with primary biliary cirrhosis (PBC), a chronic and progressive disease of the liver.
The aim of the study was to survey more thoroughly regions of the genome known to underlie other autoimmune diseases, to discover if they also play a role in PBC susceptibility.
Scientists used a DNA microchip called Immunochip in their tests: the advantage of Immunochip over genome-wide technologies is that it focuses only on regions of the genome known to be associated with an autoimmune disease, and thus captures more of the genetic variation within these regions. Immunochip can therefore be used to more thoroughly test these key candidate genes for association to a whole-host of immune-related traits, and to identify low-frequency and rare genetic variants associated with disease that would likely be missed by a microarray covering a broader range of genetic regions.
Writing in the journal Nature Genetics, the researchers outline how they identified three genetic regions associated with PBC, increasing the number of known regions associated with the disorder to 25.
By combining the results from this survey with details of gene activity from a database called ENCODE, they were able to identify which cell types are most likely to play a role in PBC.
PBC affects approximately one in a thousand women over the age of 40. The condition is characterised by inflammation in the bile ducts that blocks the flow of bile, damaging the liver cells and causing further inflammation and scarring. In severe cases, this results in the need for a liver transplant.
As there is currently no cure for PBC, treatment is focused on slowing down the progression of the disease and treating any symptoms or complications that may occur. The biological pathways underlying primary biliary cirrhosis are poorly understood, although autoimmunity, where the body attacks its own cells, is known to play a significant role.
Co-senior author of the study Dr Carl Anderson from the Wellcome Trust Sanger Institute comments: 'Previous genetic screens have identified 22 regions of the genome underlying PBC risk, and many of these are known to play a role in other autoimmune diseases, such as multiple sclerosis and type I diabetes. Using the Immunochip we were able to perform a much more thorough screen of the genomic regions previously associated with other autoimmune diseases. This resulted in us identifying a further three regions involved in PBC risk and identifying additional independent signals within some of those we already knew about.'
The hope is that these results could lead to the development of a new therapeutic approach for the treatment of PBC.
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Document Reference: Liu, J. Z. et al., Dense fine-mapping study identifies novel disease loci and implicates coding and non-coding variation in primary biliary cirrhosis risk, Nature Genetics, 2012. doi:10.1038/ng.2395
Subject Index: Medicine, Health; Life Sciences; Scientific Research