Possible involvement of cytokine gene polymorphisms in fulminant hepatitis
Possible involvement of cytokine gene polymorphisms in fulminant hepatitis
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DOI：
10.1111/j.1440-1746.2007.04846.x
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发表时间：
2007-08-01
影响因子：
4.1
通讯作者：
Shiratori, Keiko
中科院分区：
文献类型：
--
作者：
Takakura, Mihoko;Tokushige, Katsutoshi;Shiratori, Keiko
背景和目的：宿主遗传因素影响重型肝炎（FH）的进展。我们先前的资料显示受基因多态性影响的血清肿瘤坏死因子（TNF）-α水平显著升高。研究是否在IL-10基因的多态性，除了TNF-α和β基因多态性，可能有助于FH的发病机制。方法：我们分析了42例FH，78例急性肝炎（AM），和149名健康受试者（对照）。研究了IL-10启动子区-1028、-819、-592的多态性位点; TNF-α启动子区-1031、-863、-857、-308、-238的多态性位点;以及TNF-β第一内含子Nco 1位点。结果：FH患者TNF-β基因B2等位基因频率明显高于对照组，且与对照组相比差异有统计学意义（P < 0. 05）。TNF-α基因-1031、-863、-857、-308和-238位点多态性在三组中无差异。FH患者IL-10产生水平低的单倍型频率高于对照组，而IL-10产生水平高的单倍型频率低于对照组。IL- 10单倍型和TNF-β基因B2/B2的携带率显著高于对照组。结论：IL-10和TNF-β基因多态性可能是FH发病的重要因素。
Background and Aim: Host genetic factors have been reported as influencing the progress to fulminant hepatitis (FH). Our previous data showed the serum level of tumor necrosis factor (TNF)-alpha influenced by gene polymorphisms to be markedly increased. It was investigated whether polymorphisms in the IL-10 gene, in addition to TNF-alpha and -beta gene polymorphisms, might contribute to the pathogenesis of FH.Methods: We analyzed 42 patients with FH, 78 patients with acute hepatitis (AM), and 149 healthy subjects (control). IL-10 polymorphism sites at promoter regions -1028, -819, -592; TNF-alpha polymorphism sites at promoter regions -1031, -863, -857, -308, -238; and TNF-beta first intron Nco1 sites were studied. IL-10 gene polymorphisms were classified into three groups: low IL-10-producing haplotypes (ATA/ATA), intermediate haplotypes (ATA or CCA/CCA), and high haplotypes (ATA/ATG or CCG).Results: The allelic frequency of B2 in the TNF-beta gene was significantly higher in FH patients compared with the control group. The three groups showed no differences in polymorphisms of positions -1031, -863, -857, -308 and -238 in the TNF-alpha gene. The frequency oflowIL-10-producing haplotypes tended to be higher in FH patients compared with control and that of high IL-10-producing haplotype tended to be lower in FH patients compared with control. The carrier rate with both the IL- 10 haplotype and the TNF-beta gene B2/B2 was significantly higher than control.Conclusion: Variations of cytokine polymorphisms including IL-10 and TNF-beta genes may be attributable to the pathogenesis of FH.