Identification of the Genetic Variants Responsible for Primary Biliary Cirrhosis (PBC)

Primary biliary cirrhosis (PBC) is a disease of the liver, which predominantly affects women. It causes slowly progressive liver disease, which eventually causes liver failure, requiring a liver transplant. Several different studies of large patient cohorts indicate that the cause of this disease is likely due to a combination of factors including genetic and environmental. PBC is associated with several other "autoimmune diseases" - recently a gene has been identified to be abnormal in individuals with another autoimmune liver disease, namely rheumatoid arthritis. This gene usually tells the body when to switch off an immune response. This study plans to identify whether individuals diagnosed with PBC have a similar abnormality in this gene called protein Tyrosine Phosphatase.

Study Overview

• Status: Unknown
• Conditions: Liver Cirrhosis, Biliary; Biliary Cirrhosis, Primary

Detailed Description

Very recently, a single nucleotide polymorphism (SNP) in the PTPN22 gene encoding the Lyp (lymphoid-specific phosphatase) PTP has been shown to be associated with susceptibility to rheumatoid arthritis (RA) and Type 1 diabetes (T1D)4,5. These data are consistent with the known role for Lyp in suppressing T cell activation and with data showing T cell activation (and potentially autoreactivity) to be increased by the RA and T1D-associated PTPN22 variant. The PTPN22 risk allele has also been recently implicated in Grave's disease and as such appears to represent a susceptibility allele for many autoimmune diseases. As a number of these conditions (RA, T1D etc.) frequently occur within members of PBC families, this PTPN22 variant is very likely to also be involved in PBC, a possibility we will directly investigate in this pilot study. The aim of this study is to analyze the frequency of a specific PTPN22 polymorphism in patients with PBC.

• Study Type: Observational
• Enrollment: 500

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5T 2S8
      • Recruiting
      • Liver Clinic, Toronto Western Hospital, UHN.
      • Contact: Jenny (E.J.L.) Heathcote, MD; Phone Number: 416-603-5914
      • Principal Investigator: E. J. L. Heathcote, M.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• patients attending Liver Clinic at Toronto Western Hospital, Toronto, ON, Canada
• AMA positive and liver biopsy proven PBC.

Exclusion Criteria:

- AMA negative PBC

Study Plan

How is the study designed?

Collaborators and Investigators

• Sponsor: University Health Network, Toronto
• Investigators: Principal Investigator: E.J.L (Jenny) Heathcote, MD, UHN - Toronto Western Hospital, University of Toronto

Study record dates

Study Major Dates

• Study Start: August 1, 2004

Study Registration Dates

• First Submitted: September 2, 2005
• First Submitted That Met QC Criteria: September 2, 2005
• First Posted (Estimate): September 5, 2005

Study Record Updates

• Last Update Posted (Estimate): November 29, 2005
• Last Update Submitted That Met QC Criteria: November 28, 2005
• Last Verified: August 1, 2005

More Information

Terms related to this study

• Keywords: autoimmune disease; genes; Biliary Cirrhosis, Primary
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Liver Diseases; Biliary Tract Diseases; Bile Duct Diseases; Cholestasis, Intrahepatic; Cholestasis; Fibrosis; Liver Cirrhosis; Liver Cirrhosis, Biliary
• Other Study ID Numbers: 04-0461-AE