A Duffy antigen receptor for chemokines (DARC) polymorphism that determines pro-fibrotic chemokine serum concentrations is not directly associated with severity of hepatitis C infection

Genetic host factors influence the progression of hepatitis C infection (HCV). Chemokines play important roles in HCV-induced liver fibrosis. Recently, a single nucleotide polymorphism in the Duffy antigen receptor for chemokines (DARC) was identified which strongly determines the serum concentrations of pivotal pro-fibrotic chemokines, including CCL2. We here tested the hypothesis that this genetic variant (rs12075 A/G) is a risk factor for liver fibrosis in HCV infection. Overall, 880 patients with HCV from three cohorts and 108 controls were genotyped for rs12075. Although serum CCL2 levels were associated with early liver fibrosis, rs12075 itself was not associated with HCV infection or the severity of liver disease in any of the cohorts. The lack of association was evident in qualitative and quantitative analysis despite sufficient statistical power. We conclude that gene variations that strongly determine serum concentrations of chemokines are not necessarily risk markers of the disease traits in which these molecules play pathophysiological roles.