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TRAF1 gene polymorphism correlates with the titre of Gp210 antibody in patients with primary biliary cirrhosis.

ABSTRACT: BACKGROUND: Polymorphisms of TRAF1 (Tumor necrosis factor receptor-associated factor 1) are associated with rheumatoid arthritis (RA). Whether TRAF1 polymorphisms confer increased risk for primary biliary cirrhosis (PBC), an autoimmune liver disease which can co-exist with RA, is unknown. AIM OF THE STUDY: To assess the frequency of the RA-conferring susceptibility TRAF1 polymorphisms rs3761847 and rs2900180 in a cohort of PBC patients. The association of TRAF1 polymorphisms with clinical features and autoantibody markers was also analyzed. METHODS: We studied 179 PBC patients and 300 controls. Samples were genotyped for TRAF1 gene polymorphisms by real-time PCR. Autoantibodies were tested by ELISA. RESULTS: The frequency of rs3761847 and rs2900180 polymorphisms did not differ between patients and controls. Laboratory or clinical features were not associated with specific polymorphisms. Gp210 autoantibody titres were conspicuously higher among GG homozygotes of rs3761847 as compared with AA homozygotes (P = 0.02). In contrast, antichromatin titers were higher in AA compared to GG rs3761847 homozygotes (P = 0.04). Rheumatoid factor IgG titres were significantly higher in rs2900180 TT homozygotes than CC homozygotes (P = 0.02). CONCLUSIONS: TRAF1 polymorphisms occur with the similar frequency in PBC patients and in the general population, but their presence is probably involved in the regulation of specific PBC-related autoantibodies.

SUBMITTER: Kempinska-Podhorodecka A

PROVIDER: S-EPMC3485529 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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TRAF1 gene polymorphism correlates with the titre of Gp210 antibody in patients with primary biliary cirrhosis.

Kempinska-Podhorodecka Agnieszka A Shums Zakera Z Wasilewicz Michał M Wunsch Ewa E Milkiewicz Malgorzata M Bogdanos Dimitrios P DP Norman Gary L GL Milkiewicz Piotr P

Clinical & developmental immunology 20121022

<h4>Background</h4>Polymorphisms of TRAF1 (Tumor necrosis factor receptor-associated factor 1) are associated with rheumatoid arthritis (RA). Whether TRAF1 polymorphisms confer increased risk for primary biliary cirrhosis (PBC), an autoimmune liver disease which can co-exist with RA, is unknown.<h4>Aim of the study</h4>To assess the frequency of the RA-conferring susceptibility TRAF1 polymorphisms rs3761847 and rs2900180 in a cohort of PBC patients. The association of TRAF1 polymorphisms with cl ...[more]

PMID: 23125866

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Project description:Primary biliary cirrhosis (PBC) is an immune-mediated chronic cholestatic liver disease with a slowly progressive course. Without treatment, most patients eventually develop fibrosis and cirrhosis of the liver and may need liver transplantation in the late stage of disease. PBC primarily affects women (female preponderance 9-10:1) with a prevalence of up to 1 in 1,000 women over 40 years of age. Common symptoms of the disease are fatigue and pruritus, but most patients are asymptomatic at first presentation. The diagnosis is based on sustained elevation of serum markers of cholestasis, i.e., alkaline phosphatase and gamma-glutamyl transferase, and the presence of serum antimitochondrial antibodies directed against the E2 subunit of the pyruvate dehydrogenase complex. Histologically, PBC is characterized by florid bile duct lesions with damage to biliary epithelial cells, an often dense portal inflammatory infiltrate and progressive loss of small intrahepatic bile ducts. Although the insight into pathogenetic aspects of PBC has grown enormously during the recent decade and numerous genetic, environmental, and infectious factors have been disclosed which may contribute to the development of PBC, the precise pathogenesis remains enigmatic. Ursodeoxycholic acid (UDCA) is currently the only FDA-approved medical treatment for PBC. When administered at adequate doses of 13-15 mg/kg/day, up to two out of three patients with PBC may have a normal life expectancy without additional therapeutic measures. The mode of action of UDCA is still under discussion, but stimulation of impaired hepatocellular and cholangiocellular secretion, detoxification of bile, and antiapoptotic effects may represent key mechanisms. One out of three patients does not adequately respond to UDCA therapy and may need additional medical therapy and/or liver transplantation. This review summarizes current knowledge on the clinical, diagnostic, pathogenetic, and therapeutic aspects of PBC.

Project description:Primary biliary cirrhosis (PBC) is an autoimmune, slowly progressive, cholestatic, liver disease characterized by a triad of chronic cholestasis, circulating anti-mitochondrial antibodies (AMA), and characteristic liver biopsy findings of nonsuppurative destructive cholangitis and interlobular bile duct destruction. About 10% of PBC patients, however, lack AMA. A variant, called PBC-autoimmune hepatitis (AIH) overlap, is characterized by the above findings of PBC together with findings of elevated serum alanine aminotransferase, elevated serum immunoglobulin G, and circulating anti-smooth muscle antibodies, with liver biopsy demonstrating periportal or periseptal, lymphocytic, piecemeal necrosis. PBC is hypothesized to be related to environmental exposure in genetically vulnerable individuals. It typically occurs in middle-aged females. Prominent clinical features include fatigue, pruritis, jaundice, xanthomas, osteoporosis, and dyslipidemia. The Mayo Risk score is the most widely used and best prognostic system. Ursodeoxycholic acid is the primary therapy. It works partly by reducing the concentration and injury from relatively toxic bile acids. PBC-AIH overlap syndrome is treated with ursodeoxycholic acid and corticosteroids, especially budesonide. Obeticholic acid and fibrate are promising new, but incompletely tested, therapies. Liver transplantation is the definitive therapy for advanced disease, with about 70% 10-year survival after transplantation. Management of pruritis includes local skin care, dermatologist referral, avoiding potential pruritogens, cholestyramine, and possibly opioid antagonists, sertraline, or rifaximin. Management of osteoporosis includes life-style modifications, administration of calcium and vitamin D, and alendronate. Statins are relatively safe to treat the osteopenia associated with PBC. Associated Sjogren's syndrome is treated by artificial tears, cyclosporine ophthalmic emulsion to stimulate tear production; and saliva substitutes, cholinergic agents, and scrupulous oral and dental care. Complications of cirrhosis from advanced PBC include esophageal varices, ascites, spontaneous bacterial peritonitis, hepatorenal syndrome, and hepatoma formation.

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TRAF1 gene polymorphism correlates with the titre of Gp210 antibody in patients with primary biliary cirrhosis.

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TRAF1 gene polymorphism correlates with the titre of Gp210 antibody in patients with primary biliary cirrhosis.

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