There are three isoforms DAPT secretase Notch of TGF-�� (TGF-��1, -��2, and -��3) that are encoded by distinct genes, but have similar biologic actions (1). Of these, TGF-��1 is a major cytokine that contributes to liver fibrosis via activating hepatic stellate cells and increasing the synthesis of extracellular matrix (2). Seven genetic polymorphisms of TGF-��1 have been identified: 3 in the upstream region of the gene at positions -988, -800, and -509; 1 in a nontranslated region at position +72; 2 in the signal peptide sequence region at codon 10 (position +869 C or T) and 25 (position +915 G or C); and 1 in the protein coding region at codon 629 (3). TGF-��1 gene polymorphisms at codon 10 and 25 affect the amounts of TGF-��1 production in vivo and in vitro.
In the lungs, leucine homozygous genotype (L/L, +869 T/T) at codon 10 was associated with increased serum level of TGF-��1 and lung fibrosis (4). Arginine homozygous genotype (+915 G/G) at codon 25 was associated with in vitro increased leukocyte production of TGF-��1 and lung fibrosis (4). In the liver, arginine homozygous genotype at codon 25 was associated with liver fibrosis (5). However, genetic polymorphism at codon 10 showed conflicting results as to which genotype was more fibrogenic in the liver (5-9). These conflicting results could be attributed to the complex pathogenesis and various factors that contribute to liver fibrosis. There has been no genetic polymorphism at codon 25 in Koreans (10). Present study investigated whether the genetic polymorphism at codon 10 is associated with the development of cirrhosis in chronic HBV carriers.
MATERIALS AND METHODS Patients Two hundred and twenty Korean patients with cirrhosis (including HCC with underlying cirrhosis), who had hepatitis B surface antigen (HBsAg, RIA, Abbott Laboratory, Chicago, IL, USA) for over 6 months and no hepatitis C virus antibody (anti-HCV, RIA, General Biologicals Corp, Hsin Chu, Taiwan), were admitted to Gil Hospital, Incheon, Korea from January 2001 to January 2005. Among those, one hundred and twenty-one patients who had alcohol intake of less than 20 g/day and were over 50 yr old were assigned to liver cirrhosis (LC) group. Eighteen patients in LC group were admitted due to non liver related symptoms and diseases. The other 103 patients visited hospital due to liver related symptoms.
Diagnosis of cirrhosis was based on at least 2 of the followings: 1) gastroesophageal varices on endoscopy, 2) cirrhotic surface or regenerating nodules of liver and 3) splenomegaly by radiologic Anacetrapib images (ultrasonography or computed tomography). Eighty-four Korean chronic hepatitis B patients, who had HBsAg for over 6 months, no anti-HCV, no clinical signs of cirrhosis (above criteria), alcohol intake of less than 20 g/day and were over 50 yr old, were admitted to the same hospital during the same periods.