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基因肿瘤坏死因子多态性-308G>A(rs1800629)及其与非酒精性脂肪性肝炎患者熊去氧胆酸治疗效果的关系。

Gene TNF Polymorphism -308G>A (rs1800629) and Its Relationship with the Efficiency of Ursodeoxycholic Acid Therapy in Patients with Nonalcoholic Stetohepatitis.

作者信息

Kurbatova I V, Topchieva L V, Dudanova O P

机构信息

Institute of Biology, Karelian Research Center, Russian Academy of Sciences, Moscow, Russia.

Petrozavodsk State University, Petrozavodsk, Republic of Karelia, Russia.

出版信息

Bull Exp Biol Med. 2017 Dec;164(2):181-185. doi: 10.1007/s10517-017-3953-1. Epub 2017 Nov 27.

Abstract

Association of TNF gene polymorphism -308G>A with the development of nonalcoholic steatohepatitis in the Russian population was revealed. Carriers of allele A of the TNF gene marker -308G>A have significantly higher risk of nonalcoholic steatohepatitis development: OR=1.69 (1.05; 2.71). Allele A carriage by this marker predicts an increase in the basal HDL level and a decrease in LDL and IL-10 levels in the blood of healthy subjects. Patients with nonalcoholic steatohepatitis, differing by the TNF gene -308G>A marker genotype, differ by the time course of the markers of hepatocellular damage (ALT, AST), activity of hepatocyte apoptosis (tissue polypeptide-specific antigen), and activation of specific humoral immunity (γ-globulin) in response to therapy with ursodeoxycholic acid in a dose of 10-15 mg/kg over 4-6 weeks. Carriers of allele A of the TNF gene polymorphic marker -308G>A are more sensitive to ursodeoxycholic acid therapy than carriers of GG genotype.

摘要

在俄罗斯人群中发现肿瘤坏死因子(TNF)基因多态性-308G>A与非酒精性脂肪性肝炎的发生有关。TNF基因标记-308G>A的A等位基因携带者发生非酒精性脂肪性肝炎的风险显著更高:比值比(OR)=1.69(1.05;2.71)。该标记的A等位基因携带情况预示着健康受试者血液中基础高密度脂蛋白(HDL)水平升高,低密度脂蛋白(LDL)和白细胞介素-10(IL-10)水平降低。非酒精性脂肪性肝炎患者因TNF基因-308G>A标记基因型不同,在接受4至6周10 - 15毫克/千克剂量熊去氧胆酸治疗时,肝细胞损伤标志物(丙氨酸转氨酶、天冬氨酸转氨酶)的时间进程、肝细胞凋亡活性(组织多肽特异性抗原)以及特异性体液免疫激活(γ-球蛋白)情况存在差异。TNF基因多态性标记-308G>A的A等位基因携带者比GG基因型携带者对熊去氧胆酸治疗更敏感。

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