Correction to: Genes and Immunity (2002) 3, 359–367. doi:10.1038/sj.gene.6363883 Since the publication of the above article, an error was discovered in the genotyping assay for the exon 8 A370T SNP at position 11429 (rs11669576). The P1 and P2 probe sequences for the detection of this SNP were designed incorrectly and end one base before the polymorphic site, similarly the first base of P3 does include the SNP site itself.

Interferon stimulates the expression of a number of genes encoding enzymes with antiviral activities, including myxovirus resistance-1 (MxA), 2-5-oligoadenylate synthetase 1 (OAS-1) and double-stranded RNA-dependent protein kinase (PK R ). We examined whether polymorphisms in these genes influenced the outcome of hepatitis C virus (HCV) infection. We observed a lower frequency of the GG genotype at position −88 in the MxA gene promoter in self-limiting HCV infection (OR=0.56; 95% CI: 0.35–0.8; P =0.010) and in nonresponders to therapy (OR=0.49; 95% CI: 0.25–0.95; P =0.020). This genotype predominantly influenced the outcome of treatment in patients with viral genotype 1 (OR=0.22 95% CI: 0.07–0.67; P =0.002). A polymorphism in the 3′-untranslated region of the OAS-1 gene was associated with outcome of infection (GG genotype less frequent in self-limiting infection: OR=0.43; 95% CI: 0.21–0.86; P =0.010). A polymorphism at position −168 in the promoter region of the PKR gene was associated with self-limiting infection (CT genotype: OR=2.75; 95% CI: 1.45–5.24; P =0.002). Further associations were found with a CGG trinucleotide repeat in the 5′UTR region of the PKR gene. Polymorphisms in the interferon-induced genes, Mx A, OAS-1 and PKR appear thus associated with HCV outcome.

We studied the baseline expression level of 25 interferon-regulated genes (MxA, GPR3, IL17RC, ISG15, TRAIL, OASL, IFIT1, IFIT2, RSAD2, OAS3, IFI44L, TRIM22, IL10, CXCL10, STAT1, OAS1, OAS2, IFNAR1, IFNAR2, IFNβ, ISG20, IFI6, PKR, IRF7, USP18), recurrently proposed in the literature as predictive biomarkers of interferon-beta treatment response, in whole blood of 10 “responders” and 10 “non-responders” multiple sclerosis relapsing–remitting patients, retrospectively selected on the basis of stringent clinical criteria after a five years follow-up. However, we cannot confirm the predictive value of these candidate biomarkers.

The effect of host genetic variation on the outcome of hepatitis C virus (HCV) infection and its treatment is poorly understood. The chemokine receptors CCR5, CCR2, and CCR3 and their ligands, RANTES, MCP-1, MCP-2, and MIP-1alpha, are involved in the immune responses and the selective recruitment of lymphocytes to the liver in HCV infection. We studied 20 polymorphisms within these genes and investigated their association with persistent carriage of HCV, severity of liver disease, hepatic inflammation, and response to treatment in a large European cohort. Significant associations were found between CCR5-delta32 and reduced portal inflammation (P =.011, odds ratio [OR]: 2.3, 95% confidence interval [CI]: 1.09-4.84) and milder fibrosis (P =.015, OR: 1.97, 95% CI: 1.13-3.42). A promoter polymorphism at position -403 in the RANTES gene was associated with less severe portal inflammation (P =.004). An amino acid change in MCP2, Q46K, was associated with severity of fibrosis (P =.018, OR: 2.29, 95% CI: 1.14-4.58). In conclusion, our study suggests a possible role of the polymorphisms CCR5-delta32, RANTES -403, and MCP-2 Q46K in the outcome of HCV infection.

BACKGROUND:The rate of progression to cirrhosis varies among individuals chronically infected with the hepatitis C virus (HCV). Coagulation pathway activation in models of hepatic fibrosis suggests variation in coagulation pathway components may influence the rate of fibrosis. We hypothesised that polymorphisms of the coagulation factors II and V affect the rate of progression to cirrhosis in HCV infected subjects.METHODS:We studied the relationship between rate of fibrosis (calculated by dividing the fibrosis stage by duration of infection) and genotypes of specific coagulation pathway genes in 352 White European patients infected with HCV. Genotyping was performed using reverse line blot hybridisation.RESULTS:The rate of fibrosis was significantly higher in patients with the factor V Leiden genotype (Arg560Gln) (ANOVA, p=0.004). In disease association studies, a significant association was seen (Fisher's exact test, p=0.029; odds ratio 3.28 for fast progression to cirrhosis (expected to reach cirrhosis in less than 30 years) if heterozygous for factor V Leiden). No associations were seen between factor II genotype and fibrosis rate.CONCLUSIONS:Possession of the factor V Leiden polymorphism significantly increases the risk of rapid disease progression in HCV, suggesting a role for the coagulation system in the pathogenesis of fibrotic liver disease.

Hepatitis C virus (HCV) infection is very common worldwide, but has a broad range of outcomes. A minority of patients are able to clear infection spontaneously, and this is thought to be due to the emergence and maintenance of effective cell-mediated immunity, particularly CD4+ T lymphocyte responses. Furthermore, genetic studies have indicated that HLA class II genotype strongly influences the outcome of infection. We have therefore investigated the influence of the protective HLA class II haplotype (DQB1*0301, which is in tight linkage disequilibrium with DRB1*1101) on the CD4+ T lymphocyte responses to HCV. We observe a strong association between this genotype and maintenance of a multispecific CD4+ T helper response. The effect on T helper responses was also maintained after combination interferon-alpha/ribavirin therapy, although the latter influenced the pattern of viral antigens to which patients responded. This is the first disease in which an association of HLA genotype with clinical outcome has been linked to an alteration of the immunological phenotype. The selection of protective peptides in those with the favourable HLA class II genotype may point in the direction of suitable vaccine candidates.

cirrhosis=LC) and 47 patients with non-HCV liver diseases= LD-NC(26 chronic hepatitis=CH-NC, 21 LC).26 normal liver samples served as control.Student's t-test and Pearson's correlation test were used for statistical analysis.Results:A significantly higher(p<0.05)propotion of cells were in Gl phase in LD-C(94±4)than in LD-NC(Gl:90±6) suggesting a decreased hepatocyte proliferation.The lower ratio of PF(O.Ol ±0.02) in LD-C may suggest that the regeneration process was blocked by HCV.There were significant differences(p<0.05) in DI,G1,S,G2 and PF between CH-C(DI: 1.l0±0.05,Gl:94±4,S:3.6±3.2,G2:2.2±2.l,PF:0.OI ±0.02) and CH-NC(DI: 1.06±0.06,GI:90±6,S:6.4±6.0,G2:3.4±2.8,PF:0.03±0.04).There was no difference in the 5 measured parameters among the subgroups of LD-C.We found DNA aneuploidy in LD-C(DI:1.11±0.05).Conclusion:HCV causes DNA aneuploidy by blocking cell proliferation and hepatocellular regeneration.This may in certain conditions lead to the malignant transformation of hepatocytes.