Chronic hepatitis C (HCV) represents one of the most common
chronic infections worldwide and is a major indication for
liver transplantation. Liver
inflammation is the main predictor of advanced
fibrosis in HCV. Inflammatory cells are recruited to the liver by
chemokines. Recently, a novel class of
chemokine receptors has been characterized that lack signaling functions and are termed
scavenger receptors. We determine here whether genetic variations of the
scavenger receptor D6 contribute to the grade of liver
inflammation in HCV. Four haplotype tagging single nucleotide polymorphisms (SNPs) were identified from HapMap that cover the genetic information of D6 (CCBP2). Among these SNPs, rs4683336 was associated with liver
inflammation in qualitative (p = 0.003) and quantitative (p = 0.0086) genotype analysis. This association was confirmed in an independent cohort of HCV-infected patients (p = 0.006 for qualitative and p = 0.0046 for quantitative analysis, respectively). Furthermore, the haplotype that is tagged by marker rs4683336 was significantly correlated with liver
inflammation when compared with the most common D6 haplotype (p = 0.014). The importance of genetic variations in D6 was supported through the demonstration of an association of D6
mRNA expression with histologic
inflammation in liver biopsies and a considerable range of D6
mRNA expression in isolated human hepatocytes. In conclusion, we demonstrate that variations in a
chemokine scavenging receptor are significantly correlated with clinical inflammatory phenotypes such as HCV
infection.