CD14基因多态性对酒精性肝病和慢性丙型肝炎感染患者疾病转归的不同影响。
Different effects of a CD14 gene polymorphism on disease outcome in patients with alcoholic liver disease and chronic hepatitis C infection.
作者信息
Meiler C, Muhlbauer M, Johann M, Hartmann A, Schnabl B, Wodarz N, Schmitz G, Scholmerich J, Hellerbrand C
机构信息
Department of Internal Medicine I, University of Regensburg, Regensburg D-93042, Germany.
出版信息
World J Gastroenterol. 2005 Oct 14;11(38):6031-7. doi: 10.3748/wjg.v11.i38.6031.
AIM
Clinical and experimental data suggest that gut-derived endotoxins are an important pathogenic factors for progression of chronic liver disease. Recently, a C-T (-159) polymorphism in the promoter region of the CD14 gene was detected and found to confer increased CD14 expression and to be associated with advanced alcoholic liver damage. Here, we investigated this polymorphism in patients with less advanced alcoholic liver disease (ALD) and chronic hepatitis C virus (HCV) infection.
METHODS
CD14 genotyping was performed by PCR-RFLP analysis in (a) 121 HCV patients, (b) 62 patients with alcohol-associated cirrhosis (Alc-Ci), (c) 118 individuals with heavy alcohol abuse without evidence of advanced liver damage (Alc-w/o Ci), and (d) 247 healthy controls. Furthermore, serum levels of soluble CD14 (sCD14) and transaminases were determined.
RESULTS
The TT genotype was significantly more frequent in Alc-Ci compared to Alc-w/o Ci or controls (40.3% vs 23.7% or 24.0%, respectively). In Alc-w/o Ci, serum levels of transaminases did not differ significantly between patients with different CD14 genotypes. In HCV patients, TT-homozygotes had significantly higher sCD14 levels and sCD14 serum levels were significantly higher in patients with advanced fibrosis or cirrhosis. However, no association was found between CD14 genotypes and histological staging or grading.
CONCLUSION
Considering serum transaminases as surrogate markers for alcoholic liver damage, the CD14 polymorphism seems to exhibit different effects during the course of ALD. Differences in genotype distribution between cirrhotic HCV patients and alcoholics and the known functional impact of this polymorphism on CD14 expression levels further indicate differences in the pathophysiological role of CD14 and CD14-mediated lipopolysaccharides signal transduction with regard to the stage as well as the type of the underlying liver disease.
目的
临床和实验数据表明，肠道源性内毒素是慢性肝病进展的重要致病因素。最近，在CD14基因启动子区域检测到一种C-T（-159）多态性，发现其可导致CD14表达增加，并与晚期酒精性肝损伤相关。在此，我们研究了病情较轻的酒精性肝病（ALD）和慢性丙型肝炎病毒（HCV）感染患者中的这种多态性。
方法
通过聚合酶链反应-限制性片段长度多态性分析（PCR-RFLP）对以下人群进行CD14基因分型：（a）121例HCV患者，（b）62例酒精相关性肝硬化（Alc-Ci）患者，（c）118例有严重酒精滥用但无晚期肝损伤证据（Alc-w/o Ci）的个体，以及（d）247名健康对照者。此外，还测定了可溶性CD14（sCD14）和转氨酶的血清水平。
结果
与Alc-w/o Ci或对照组相比，Alc-Ci患者中TT基因型的频率显著更高（分别为40.3%、23.7%或24.0%）。在Alc-w/o Ci患者中，不同CD14基因型患者的血清转氨酶水平无显著差异。在HCV患者中，TT纯合子的sCD14水平显著更高，且晚期纤维化或肝硬化患者的sCD14血清水平显著更高。然而，未发现CD14基因型与组织学分期或分级之间存在关联。
结论
将血清转氨酶作为酒精性肝损伤的替代标志物，CD14多态性在ALD病程中似乎表现出不同的作用。肝硬化HCV患者和酗酒者之间基因型分布的差异以及该多态性对CD14表达水平的已知功能影响，进一步表明CD14和CD14介导的脂多糖信号转导在潜在肝病的阶段和类型方面的病理生理作用存在差异。
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