Squamous cell carcinoma antigen-1 (SERPINB3) polymorphism in chronic liver disease

Abstract Background The serpin squamous cell carcinoma antigen (SCCA, SERPINB3) has been found over-expressed in primary liver cancer and at lower extent in cirrhosis and chronic hepatitis. A novel SCCA-1 variant (SCCA-PD), presenting a single mutation in the reactive centre (Gly351Ala), has been re...

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Published in:Digestive and liver disease 2009-03, Vol.41 (3), p.212-216
Main Authors: Turato, C, Ruvoletto, M.G, Biasiolo, A, Quarta, S, Tono, N, Bernardinello, E, Beneduce, L, Fassina, G, Cavalletto, L, Chemello, L, Merkel, C, Gatta, A, Pontisso, P
Format: Article
Language:English
Subjects:
Adult
Antigens, Neoplasm - genetics
Antigens, Neoplasm - immunology
Case-Control Studies
Chronic Disease
Female
Fibrosis
Gastroenterology and Hepatology
Humans
Immunoglobulin M - blood
Liver disease progression
Liver Diseases - genetics
Male
Middle Aged
Polymorphism, Restriction Fragment Length
SCCA polymorphism
Serpins
Serpins - genetics
Serpins - immunology
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Summary:Abstract Background The serpin squamous cell carcinoma antigen (SCCA, SERPINB3) has been found over-expressed in primary liver cancer and at lower extent in cirrhosis and chronic hepatitis. A novel SCCA-1 variant (SCCA-PD), presenting a single mutation in the reactive centre (Gly351Ala), has been recently identified (rs3180227). Aim To explore SCCA-1 polymorphism in patients with HCV infection as single etiologic factor and different extent of liver disease. Methods One hundred and fourty-eight patients with chronic HCV infection (45 chronic hepatitis, 53 cirrhosis, 50 HCC) and 50 controls were evaluated. SCCA-1 polymorphism was studied by restriction fragment length polymorphism and confirmed randomly by direct sequencing. Circulating SCCA–IgM complex was determined by ELISA. Results SCCA-PD was detected with higher frequency in cirrhotic patients (45.3%, odds ratio = 2.62; 95%CI 1.13–6.10, p = 0.038) than in patients with chronic hepatitis or in controls (24.4% and 24%, respectively). Intermediate figures were found in hepatocarcinoma (36.0%). SCCA–IgM in serum was lower in patients carrying SCCA-PD than in wild type patients and the difference was statistically significant in cirrhotic patients (mean ± S.D. = 117.45 ± 54.45 U/ml vs. 268.52 ± 341.27 U/ml, p = 0.026). Conclusions The newly identified SCCA-PD variant was more frequently found in liver cirrhosis, suggesting that patients carrying this polymorphism are more prone to develop progressive liver fibrosis.
ISSN:1590-8658
1878-3562
DOI:10.1016/j.dld.2008.06.001