Association of genetic polymorphisms of chemokines and their receptors with clearance or persistence of hepatitis C virus infection.

BACKGROUND: Polymorphisms of certain genes may have an effect on either persistence of infection or spontaneous clearance of hepatitis C virus (HCV). We hypothesized that one or more variants of chemokines (CCL2 and CCL5) and chemokine receptors (CC chemokine receptor type 2 [CCR2]) genes are associated with the susceptibility to HCV infection.

METHODS: We recruited 1460 patients with chronic HCV (CHC), 108 subjects with spontaneous virus clearance (SVC) and 1446 individuals as a healthy control group. All were genotyped for single nucleotide polymorphisms: rs13900 C/T of CCL2, rs3817655 T/A of CCL5 and rs743660 G/A and rs1799864 G/A of CCR2 using allelic discrimination real-time PCR technique.

RESULTS: The carriage of the A allele of CCR2 rs743660 was significantly higher in CHC compared to SVC (odds ratio [OR] 4.03) and to controls (1.42) and in controls compared to SVC (2.85) (all P < 0.01). Similarly, the A allele of CCR2 rs1799864 was significantly higher in the CHC group when compared with both SVC (1.97) and controls (2.13) (both P < 0.01), but the OR between controls and SVC was not significant (1.08, P = 0.723). Carriage of C allele of CCL2 rs13900 and the T allele of CCL5 rs3817655 were significantly higher in SVC group when compared with both CHC (OR = 0.19 and OR = 0.24, respectively) and control groups (OR = 0.65 and OR = 0.45, respectively [all P < 0.01]).

CONCLUSIONS: Susceptibility to HCV infection is associated with A alleles of both (rs743660 and rs1799864 G/A) of CCR2 while spontaneous clearance of HCV is associated with the C allele of rs13900 of CCL2 and T allele of rs3817655 of CCL5.