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 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. © 2008 Editrice Gastroenterologica Italiana S.r.l.