HLA-G 3'UTR haplotype analyses in HCV infection and HCV-derived cirrhosis, hepatocellular carcinoma and fibrosis.

Abstract

Hepatitis C virus (HCV) infection is a major cause of chronic liver disease. Chronic HCV infection is also an important cause of hepatic fibrosis, cirrhosis and hepatocellular carcinoma (HCC). HCV has the capacity to evade immune surveillance by altering the host immune response. Moreover, variations in immune-related genes can lead to differential susceptibility to HCV infection as well as interfere on the susceptibility to the development of hepatic fibrosis, cirrhosis and HCC. The human leucocyte antigen G (HLA-G) gene codes for an immunomodulatory protein known to be expressed in the maternal-foetal interface and in immune-privileged tissues. The HLA-G 3' untranslated region (3'UTR) is important for mRNA stability, and variants in this region are known to impact gene expression. Studies, mainly focusing in a 14bp insertion/deletion polymorphism, have correlated HLA-G 3'UTR with susceptibility to viral infections, but other polymorphic variants in the HLA-G 3'UTR might also affect HCV infection as they are inherited as haplotypes. The present study evaluated HLA-G 3'UTR polymorphisms and performed linkage disequilibrium test and haplotype assembly in 286 HCV infected patients who have developed fibrosis, cirrhosis or HCC, as well as in 129 healthy control subjects. Haplotypes UTR-1, UTR-2 and UTR-3 were the most observed in HCV+ patients, in the frequencies of 0.276, 0.255 and 0.121, respectively. No statistically significant difference was observed between HCV+ and control subjects, even when patients were grouped according to outcome (HCC, cirrhosis or fibrosis). Despite that, some trends in the results were observed, and therefore, we cannot rule out the possibility that variants associated to high HLA-G expression can be involved in HCV infection susceptibility.