Abstract
Background and AimsVitamin D exerts immunomodulatory effects on the host response against infection with hepatitis C virus (HCV). This study was performed to assess the putative influence of polymorphisms in vitamin D-related genes on the response to antiviral therapy in patients with chronic hepatitis C (CHC).MethodsSingle nucleotide polymorphisms (SNPs) in CYP27B-1260 gene promoter (rs10877012AC) and in vitamin D receptor (VDR) gene rs2228570TC, rs1544410CT, rs7975232AC and rs731236AT were analyzed in a cohort of 238 Caucasian CHC patients treated with pegylated interferon (Peg-IFN) plus ribavirin (RBV). Multivariate analyses were performed to exclude confounding effects of well-known baseline predictors of response to therapy (HCV genotype and load, IL28B genotype, age, and GGT and serum cholesterol).ResultsThree SNPs at the VDR gene (rs1544410, rs7975232 and rs731236) were in strong linkage disequilibrium, with the CCA haplotype predicting therapeutic failure [Odds ratio 2.743; (95% C.I. 1.313–5.731), p = 0.007]. The carrier state of the VDR rs2228570 T allele was inversely related to the probability of therapeutic failure [Odds ratio 0.438; 95 C.I. (0.204–0.882), p = 0.021]. No relation existed between CYP27B-1260 rs10877012 polymorphism and response to therapy. The area under the operating curve (AUROC) based on the model including all variables significantly related to the response to therapy was 0.846 (95% confidence interval = 0.793–0.899).Conclusion VDR gene polymorphisms are independently related to the response to Peg-IFN+RBV therapy in chronic hepatitis C and could be used as complementary biomarkers of response when included in a prediction algorithm in association with demographic, virologic, biochemical and genetic traits.
Highlights
The success rate of current therapy for chronic hepatitis C (CHC) that combines pegylated interferon plus ribavirin is related to a variety of predictive factors that can be used as response biomarkers
Patients The population study included all patients with CHC who were scheduled to receive combined double therapy with pegylated interferon and ribavirin in accordance with current guidelines [19], and who attended since June 2003 to the outpatient clinic of the Gastroenterology Department (Liver Unit), San Carlos University Hospital, Madrid, Spain, Only patients who had completed a full course of therapy or who had stopped therapy due to therapeutic failure, defined with widely accepted criteria [19], were included in the study
Three of the four SNPs at the vitamin D receptor (VDR) gene were in strong linkage disequilibrium and patients were categorized as non carriers/carriers of the allelic combination rs1544410C - rs7975232C - rs731236A, defined as the risk haplotype in agreement with previously published evidence [14]
Summary
The success rate of current therapy for chronic hepatitis C (CHC) that combines pegylated interferon plus ribavirin is related to a variety of predictive factors that can be used as response biomarkers. Some of these depend on the hepatitis C virus (HCV), such as viral genotype, changes in critical regions of the viral genome and viral load. Vitamin D exerts immunomodulatory effects on the host response against infection with hepatitis C virus (HCV). This study was performed to assess the putative influence of polymorphisms in vitamin D-related genes on the response to antiviral therapy in patients with chronic hepatitis C (CHC)
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