TLL1 rs17047200 Increases the Risk of Fibrosis Progression in Caucasian Patients With Chronic Hepatitis C.

Abstract

We read with interest the Matsuura et al1 genome-wide association study (GWAS) of 456 Japanese patients identifying tolloid like 1 (TLL1) as a novel susceptibility locus for hepatocellular carcinoma (HCC) after clearance of hepatitis C virus (HCV) with interferon-based treatment. Although detailed functional mechanisms were not defined, the authors suggested that the TLL1 rs17047200 single nucleotide polymorphism or other intronic variants in strong LD may influence splicing, resulting in production of a catalytically more active short isoform (TLL1 isoform 2). The paper went on to suggest that the effect of the single nucleotide polymorphism was likely indirect, mediated via an impact on liver fibrosis. As evidence, there was a strong association between hepatic TLL1 messenger RNA expression and fibrosis in human and murine models. However, rs17047200 genotype distribution did not differ according to fibrosis stage.