Department of Gastroenterology, Heilongjiang Province Hospital, Harbin 150036, China.
Acta Biochim Biophys Sin (Shanghai). 2012 Aug;44(8):712-8. doi: 10.1093/abbs/gms046. Epub 2012 Jun 13.
Tumor necrosis factor-α (TNF-α) plays an important role in the pathogenesis and clinical outcome of chronic hepatitis B virus (HBV) infection. The objective of this study was to evaluate the relationship between functional polymorphisms of TNF-α and different outcomes of persistent HBV infection in a northeast Chinese Han population. Here 189 HBV spontaneously recovered subjects (SR), 571 HBV-infected patients including 180 chronic hepatitis B (CHB), 196 liver cirrhosis (LC), and 195 hepatocellular carcinoma (HCC) individuals were enrolled in this study. All the samples were genotyped for TNF-α -857C/T and -863C/A using the polymerase chain reaction-restriction fragment length polymorphism method. The frequency of -857CC genotype was significantly higher in CHB and LC individuals compared with that of SR subjects (P= 0.03, OR = 1.57, 95% CI 1.04-2.39 and P= 0.03, OR = 1.57, 95% CI 1.04-2.35, respectively). A significant difference in the distribution of the allele -857C was observed for both CHB vs. SR (P= 0.01, OR = 1.52, 95% CI 1.08-2.13) and LC vs. SR (P= 0.02, OR = 1.47, 95% CI 1.06-2.04) cohorts. In addition, the frequency of -863AA genotype was significantly higher in CHB and LC patients than that of SR subjects (P= 0.01, OR = 3.90, 95% CI 1.35-11.23 and P= 0.01, OR = 3.83, 95% CI 1.34-10.96, respectively), and allele -863A frequency was significantly more common in CHB, LC, and HCC cohorts than that of SR controls (P= 0.004, OR = 1.72, 95% CI 1.19-2.50; P= 0.001, OR = 1.81, 95% CI 1.26-2.61 and P= 0.001, OR = 1.90, 95% CI 1.33-2.73, respectively). Our data also revealed that haplotype CA was strongly associated with persistent HBV infection. These results suggest an association between the TNF-α promoter variants and different outcomes of persistent HBV infection in the studied population.
肿瘤坏死因子-α（TNF-α）在慢性乙型肝炎病毒（HBV）感染的发病机制和临床转归中起着重要作用。本研究旨在评估 TNF-α功能多态性与东北汉族人群持续 HBV 感染不同结局之间的关系。本研究共纳入 189 例 HBV 自然恢复（SR）患者、571 例 HBV 感染患者，包括 180 例慢性乙型肝炎（CHB）、196 例肝硬化（LC）和 195 例肝细胞癌（HCC）患者。所有样本均采用聚合酶链反应-限制性片段长度多态性方法对 TNF-α-857C/T 和-863C/A 进行基因分型。与 SR 患者相比，CHB 和 LC 患者的-857CC 基因型频率明显更高（P=0.03，OR=1.57，95%CI 1.04-2.39 和 P=0.03，OR=1.57，95%CI 1.04-2.35）。CHB 与 SR（P=0.01，OR=1.52，95%CI 1.08-2.13）和 LC 与 SR（P=0.02，OR=1.47，95%CI 1.06-2.04）相比，等位基因-857C 的分布差异均有统计学意义。此外，CHB 和 LC 患者的-863AA 基因型频率明显高于 SR 患者（P=0.01，OR=3.90，95%CI 1.35-11.23 和 P=0.01，OR=3.83，95%CI 1.34-10.96），等位基因-863A 频率在 CHB、LC 和 HCC 患者中均明显高于 SR 对照组（P=0.004，OR=1.72，95%CI 1.19-2.50；P=0.001，OR=1.81，95%CI 1.26-2.61 和 P=0.001，OR=1.90，95%CI 1.33-2.73）。我们的数据还表明，CA 单倍型与持续 HBV 感染密切相关。这些结果提示 TNF-α 启动子变异与研究人群中持续 HBV 感染的不同结局之间存在关联。
