Department of Biochemistry and Molecular Biology, University of Extremadura, Cáceres, Spain.
PLoS One. 2013 Sep 20;8(9):e74764. doi: 10.1371/journal.pone.0074764. eCollection 2013.
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).
Single 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).
Three 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).
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.
维生素 D 对宿主针对丙型肝炎病毒（HCV）感染的免疫反应具有免疫调节作用。本研究旨在评估维生素 D 相关基因中的单核苷酸多态性（SNP）对慢性丙型肝炎（CHC）患者抗病毒治疗反应的潜在影响。
在接受聚乙二醇干扰素（Peg-IFN）加利巴韦林（RBV）治疗的 238 例高加索 CHC 患者队列中，分析了 CYP27B-1260 基因启动子（rs10877012AC）和维生素 D 受体（VDR）基因 rs2228570TC、rs1544410CT、rs7975232AC 和 rs731236AT 的 SNP。进行多变量分析以排除已知与治疗反应相关的基线预测因子（HCV 基因型和载量、IL28B 基因型、年龄、GGT 和血清胆固醇）的混杂影响。
VDR 基因中的三个 SNP（rs1544410、rs7975232 和 rs731236）处于强连锁不平衡状态，CCA 单倍型预测治疗失败[比值比 2.743；（95%可信区间 1.313-5.731），p=0.007]。VDR rs2228570 T 等位基因的携带状态与治疗失败的可能性呈负相关[比值比 0.438；95%可信区间（0.204-0.882），p=0.021]。CYP27B-1260 rs10877012 多态性与治疗反应之间不存在关系。基于与治疗反应显著相关的所有变量的模型的曲线下面积（AUROC）为 0.846（95%置信区间为 0.793-0.899）。
VDR 基因多态性与慢性丙型肝炎患者对 Peg-IFN+RBV 治疗的反应独立相关，当与人口统计学、病毒学、生化学和遗传特征相关联并包含在预测算法中时，可作为反应的补充生物标志物。
