Kusumoto Kazunori, Uto Hirofumi, Hayashi Katsuhiro, Takahama Yuka, Nakao Hiroyuki, Suruki Robert, Stuver Sherri O, Ido Akio, Tsubouchi Hirohito
Department of Internal Medicine II, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki 889-1692, Japan.
Cytokine. 2006 Apr;34(1-2):24-31. doi: 10.1016/j.cyto.2006.03.011. Epub 2006 May 15.
We investigated the effects of polymorphisms in interleukin (IL)-10 and tumor necrosis factor (TNF)-alpha on the natural course of hepatitis C virus (HCV) infection in a community-based population in Japan. A total of 460 anti-HCV antibody seropositive individuals were classified into two groups, those who were positive or negative for HCV RNA. In HCV RNA-positive individuals with at least four annual alanine aminotransferase (ALT) measurements taken between 1993 and 2003, 74 exhibited persistently normal ALT levels, while 211 had one or more elevated ALT level tests. We examined the relationships between polymorphisms in the genes encoding IL-10 (-1082, -819, -592) or TNF-alpha (-308, -238) and HCV clearance, ALT abnormalities, or serum level of type IV collagen 7S, a marker of hepatic fibrosis. These polymorphisms were equally distributed among the patient subgroups with differential HCV RNA clearances or ALT abnormalities. Serum levels of type IV collagen 7S, however, were significantly higher in individuals with an A at position -238 or -308 in the TNF-alpha gene promoter than in individuals lacking these polymorphisms. We conclude that, while the relationships between inherited variations in IL-10 or TNF-alpha expression are not associated with alterations in HCV clearance or ALT levels, TNF-alpha polymorphisms may be associated with hepatic fibrosis.
我们在日本一个以社区为基础的人群中，研究了白细胞介素（IL）-10和肿瘤坏死因子（TNF）-α基因多态性对丙型肝炎病毒（HCV）感染自然病程的影响。总共460名抗-HCV抗体血清阳性个体被分为两组，即HCV RNA阳性或阴性个体。在1993年至2003年间至少进行过4次年度丙氨酸氨基转移酶（ALT）检测的HCV RNA阳性个体中，74人ALT水平持续正常，而211人有一次或多次ALT水平检测结果升高。我们研究了编码IL-10（-1082、-819、-592）或TNF-α（-308、-238）的基因多态性与HCV清除、ALT异常或IV型胶原7S血清水平（肝纤维化标志物）之间的关系。这些多态性在HCV RNA清除或ALT异常情况不同的患者亚组中分布相同。然而，TNF-α基因启动子中-238或-308位为A的个体，其IV型胶原7S血清水平显著高于缺乏这些多态性的个体。我们得出结论，虽然IL-10或TNF-α表达的遗传变异与HCV清除或ALT水平的改变无关，但TNF-α多态性可能与肝纤维化有关。
