Clinical Trial: Family Studies in Primary Biliary Cirrhosis (PBC)

Study Status: Completed
Recruit Status: Unknown status
Study Type: Observational

Official Title: Family Studies in Primary Biliary Cirrhosis

Brief Summary: Primary biliary cirrhosis (PBC) is a chronic liver disease primarily affecting middle age women. It is characterized by immune-mediated damage to cells lining the tiny bile ducts within the liver. Although the underlying cause of PBC is likely to be multifactorial, the epidemiologic/population data indicate a very important role for genetic predisposition, meaning that the disease seems to run in families. Susceptibility genes for PBC have not been identified possibly due to limitations such as small sample size in prior studies. The primary objective of this study is to identify these genes. This study involves obtaining clinical and demographic data as well as collecting DNA samples from patients and their parents, and siblings to screen for a select set of candidate genes as well as the full genome for variants associated with PBC.

Detailed Summary:

This proposal is predicated on cumulative data revealing a major role for genetic factors in PBC and the recent positional cloning of genes for Crohn’s disease, type 2 diabetes and rheumatoid as well as psoriatic arthritis data provide the “proof-of-principle” that susceptibility genes for multigenic diseases can be identified by linkage and association strategies. Our group has access to >600 patients with PBC and these individuals plus family members provide an excellent resource for PBC gene discovery. Moreover, an International PBC Consortium we have initiated will serve not only to validate our findings but also to serve as a source for additional patient accrual should we be searching for genes with very small effects. Thanks to the remarkable advances in genotyping technology and sequence data emanating from the Human Genome Project, patient populations such as ours can now be fully mined so as to identify susceptibility genes for common multigenic diseases. By combining the patient resources of our group and that of other Canadian centers with available knowledge of the full genome sequence and the extensive information on SNPs within this sequence, as well as our expertise in high throughput genotyping and rapid computational approaches of genetic data, we are very well positioned to begin delineating the susceptibility alleles for PBC. As such alleles are identified, the information will then be used to define the molecular pathophysiology of this disease, to determine whether genetic markers can be used to predict risk and/or stratify patients in relation to prognosis and drug responsiveness, and ultimately, to identify novel targets for improved therapeutic intervention.

For the purposes of this study only patients with a definite diagnosis of PBC will be recruited ie:- those that had an elevated serum alkaline phosphatase level and positi
Sponsor: University Health Network, Toronto

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Information By: University Health Network, Toronto

Dates:
Date Received: October 18, 2005
Date Started: October 2005
Date Completion:
Last Updated: January 13, 2006
Last Verified: October 2005