Tumor necrosis factor alpha promoter polymorphisms at position -308 in Taiwanese chronic hepatitis C patients treated with interferon-alpha.
Tumor necrosis factor alpha promoter polymorphisms at position -308 in Taiwanese chronic hepatitis C patients treated with interferon-alpha.
复制标题
接受α干扰素治疗的台湾慢性丙型肝炎患者中-308位肿瘤坏死因子α启动子多态性。
作者：
Ming‐Lung Yu;C. Dai;Chao;Li‐Po Lee;Zu;Shinn;M. Hsieh;L. Wang;Chung;W. Chuang;W. Chang
肿瘤坏死因子α启动子（TNF308.2）-308位的G-to-A多态性序列可能与疾病易感性相关。为了调查 -308 TNF-α 变异与丙型肝炎病毒 (HCV) 感染发病机制以及对慢性丙型肝炎 (CHC) 干扰素 - α (IFN-α) 治疗的反应之间的关联，在 100 名接受 IFN-α 治疗的无关台湾 CHC 患者和 100 名无关健康受试者中测定了 -308 TNF-α 基因型。 CHC 患者和对照组之间 -308 TNF-α 基因型的分布没有差异。具有不同-308 TNF-α基因型的CHC患者的年龄、性别、HCV基因型和肝脏组织病理学的坏死性炎症活性没有差异。尽管治疗前HCV RNA血清水平、转氨酶和严重纤维化发生率随着TNF308.2拷贝数的增加而降低，但差异并未达到显着性。我们未能证明 -308 TNF-α 启动子多态性与 IFN 治疗反应之间存在任何关联，通过使用多变量分析，IFN 治疗反应与肝硬化、治疗前血清 HCV RNA 水平和基因型 1b 呈负相关。总之，我们的研究结果表明，-308 TNF-α 启动子多态性在 HCV 感染的易感性和发病机制以及 CHC 对干扰素 α 治疗的反应中不起直接作用。
A G-to-A polymorphic sequence at position -308 in the tumor necrosis factor alpha promoter (TNF308.2) might be associated with disease susceptibilities. To investigate the association between -308 TNF-alpha variants and pathogenesis of hepatitis C virus (HCV) infection and response to interferon-alpha (IFN-alpha) treatment for chronic hepatitis C (CHC), -308 TNF-alpha genotypes were determined in 100 unrelated Taiwanese CHC patients treated with IFN-alpha and in 100 unrelated healthy subjects. The distribution of -308 TNF-alpha genotypes did not differ between CHC patients and controls. Age, sex, HCV genotype, and the necroinflammatory activity of liver histopathology did not differ among CHC patients with different -308 TNF-alpha genotypes. Although pretreatment HCV RNA serum levels, aminotransferase and the rate of severe fibrosis decreased with the copy number of TNF308.2, the difference did not reach significance. We failed to demonstrate any association between -308 TNF-alpha promoter polymorphisms and response to IFN therapy, which was inversely correlated to liver cirrhosis, pretreatment serum HCV RNA levels and genotype 1b by using multivariate analysis. In conclusion, our findings suggest that -308 TNF-alpha promoter polymorphisms do not play a direct role in the susceptibility and pathogenesis of HCV infection, and in the response to interferon-alpha therapy for CHC.