TGF-β1 genotypes in cirrhosis: Relationship with the occurrence of liver cancer

Abstract

This study aimed to verify whether specific single nucleotide polymorphisms (SNPs) of the transforming growth factor-β1 (TGF-β1) may predispose to end-stage liver disease and/or hepatocellular carcinoma (HCC). One hundred eighty-eight consecutive patients transplanted for liver cirrhosis (HBV N = 21, HCV N = 68, alcoholic N = 55 and others N = 23) and a control group of 140 healthy blood donors were investigated. Four SNPs were studied by restriction fragment length assays: −800G > A, −509C > T, Leu10Pro and Arg25Pro. Patients were found to possess the −509T/∗ (TT 53/188, CT 85/188, CC 50/188 vs TT 22/140, CT 61/140, CC 57/140; p < 0.002) and Arg25Pro C/∗ genotypes (CC 1/188, CG 31/188, GG 156/188 vs CC 0/140, CG 13/140, GG 127/140; p < 0.05) more frequently than controls. Patients with cirrhosis complicated by HCC possessed more frequently the Leu10Pro T/∗ genotype than patients without HCC (TT 20/54, CT 26/54, CC 8/54 vs TT 31/134, CT 69/134, CC 34/134; p < 0.05). The analysis of molecular variance detected significant genotypic differentiations between controls and cirrhotics but not between cirrhotics with or without HCC. In conclusion, TGF-β1 SNPs probably facilitate the development of liver cirrhosis, while they seem to have a limited role in predicting the occurrence of HCC.