Influence of a genetic variant in the Duffy Antigen Receptor for Chemokines (DARC) on chronic liver diseases

Introduction:

Recently, the scavenger receptor DARC receptor variant Asp42Gly was identified in a genome wide association scan to be associated with monocyte chemotactic protein 1in healthy individuals (Schnabel et al. Blood 2009). We now hypothesised that this DARC variant may be associated with susceptibility to chronic hepatitis C virus (HCV) infection and liver stiffness.

Patients and methods:

Overall, 885 patients were included in the study. Most of the patients (N=520) were anti-HCV positive (+); 365 non-infected patients suffered from other chronic liver diseases. Liver fibrosis was assessed by transient elastography. Patients were stratified according to liver stiffness values into a non-significant fibrosis group (<7.5 kPa) and a significant fibrosis group (≥ 7.5 kPa). DARC genotypes were determined using a 5'-fluorescent dye labelled exonuclease assays.

Results:

No differences in allele or genotype frequencies were detected between HCV (+) patients and patients with other chronic liver diseases. In HCV (+) patients, we did not detect an association between responders or non-responders to interferon-based antiviral therapies. Liver stiffness was also not associated with DARC genotypes, regardless of the underlying liver disease. Of note, when comparing genotype frequencies between patients with autoimmune liver diseases (AIH, PBC, PSC; N=66) with non-autoimmune liver diseases (N=651), the minor allele of the Asp42Gly variant was over-represented significantly in patients with autoimmune liver diseases (0.53 vs. 0.42; Armitage's trend test: OR=1.5, p=0.016).

Conclusions:

Although the recently identified DARC variant has functional relevance by modifying MCP-1 levels, an impact of this variant on the course or the susceptibility to chronic liver diseases appears unlikely. However, the variant may represent a risk factor for susceptibility to autoimmune liver diseases.