BACKGROUND Vitamin D derivatives and their receptor (VDR) are potent modulators of immune responses in various diseases including malignancies as well as in metabolic and infectious disorders. The impact of vitamin D receptor polymorphisms on clinical outcomes of hepatitis B virus (HBV) infection is not well understood. This study aims to investigate the potential role of VDR polymorphisms (TaqI, FokI, ApaI, and BsmI) in Vietnamese HBV infected patients and to correlate these polymorphisms with the progression of HBV-related liver disease. METHODS Four hundred forty-three HBV infected patients of the three clinically well-defined subgroups chronic hepatitis B (CHB, n = 183), liver cirrhosis (LC, n = 89) and hepatocellular carcinoma (HCC, n = 171) and 238 healthy individuals (HC) were enrolled. VDR polymorphisms were genotyped by DNA sequencing and in-house validated ARMS assays. Logistic regression models were applied in order to determine the association of VDR polymorphisms with manifest HBV infection as well as with progression of related liver diseases mulin different genetic models. RESULTS The VDR ApaI CA genotype was less frequent in HCC than in CHB patients in different genetic models (codominant model, OR = 0.5, 95%CI = 0.3-0.84, P = 0.004; dominant model, OR = 0.46, 95%CI = 0.27-0.76, P = 0.0023). In the recessive model, the genotype ApaI AA was found more frequently among HCC compared to CHB patients (OR = 2.56, 95%CI = 1.01-6.48, P = 0.04). Similarly, the ApaI CA genotype was less frequent in HCC than in non-HCC group codominant model, OR = 0.6, 95%CI = 0.4-0.98, dominant model, P = 0.04 and OR = 0.6, 95%CI = 0.38-0.90, P = 0.017). The ApaI genotypes CA and AA was significantly associated with higher levels of liver enzymes, bilirubin, and HBV DNA (P < 0.05). No association between TaqI, FokI and BsmI polymorphisms and any clinical outcome as well as liver disease progression was found. CONCLUSIONS Among the four investigated VDR polymorphisms, ApaI is associated with clinical outcome and liver disease progression in Vietnamese HBV infected patients.

中文翻译：

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越南慢性乙型肝炎病毒感染患者的维生素D受体ApaI多态性与肝脏疾病的进展有关。

背景技术维生素D衍生物及其受体（VDR）是包括恶性肿瘤在内的各种疾病以及代谢和感染性疾病中免疫应答的有效调节剂。维生素D受体多态性对乙型肝炎病毒（HBV）感染的临床结局的影响尚不清楚。这项研究旨在调查越南乙肝病毒感染患者中VDR多态性（TaqI，FokI，ApaI和BsmI）的潜在作用，并将这些多态性与HBV相关肝病的进展相关联。方法在临床上明确定义的三个亚组中，慢性乙型肝炎（CHB，n = 183），肝硬化（LC，n = 89）和肝细胞癌（HCC，n = 171）和238名健康患者中的443例HBV感染患者招募个人（HC）。通过DNA测序和经过内部验证的ARMS分析对VDR多态性进行基因分型。应用逻辑回归模型来确定VDR多态性与明显的HBV感染以及与不同遗传模型相关的肝病进展的相关性。结果在不同遗传模型中，HCC的VDR ApaI CA基因型的发生率低于CHB患者（显性模型，OR = 0.5，95％CI = 0.3-0.84，P = 0.004；显性模型，OR = 0.46，95％CI = 0.27-0.76，P = 0.0023）。在隐性模型中，与CHB患者相比，在肝癌中发现ApaI AA基因型的频率更高（OR = 2.56，95％CI = 1.01-6.48，P = 0.04）。同样，与非HCC组显性模型相比，HCC中ApaI CA基因型的频率较低，OR = 0.6，95％CI = 0.4-0.98，显性模型，P = 0.04和OR = 0.6，95％CI = 0.38-0.90 ，P = 0.017）。ApaI基因型CA和AA与肝酶，胆红素和HBV DNA的较高水平显着相关（P <0.05）。没有发现TaqI，FokI和BsmI多态性与任何临床结果以及肝病进展之间存在关联。结论在四个调查的VDR多态性中，ApaI与越南HBV感染患者的临床结局和肝病进展有关。