Askar Eva, Ramadori Giuliano, Mihm Sabine
Department of Gastroenterology and Endocrinology, University Medical Center, Georg-August-University, Robert-Koch-Strasse 40, D-37075 Goettingen, Germany.
World J Gastroenterol. 2009 Aug 21;15(31):3884-90. doi: 10.3748/wjg.15.3884.
To analyze the correlation between CD14 rs2569190/C-159T single nucleotide polymorphism (SNP) and disease progression in chronic hepatitis C.
Liver biopsy specimens from a total of 137 and 349 patients with chronic hepatitis C were separately evaluated with respect to necroinflammatory activity (grading) and architectural changes (staging). In one group, further histological lesions characteristic for hepatitis C, hepatitis C virus subtypes, and biochemical parameters of liver disease were also investigated. Samples of genomic DNA were genotyped for the respective SNP by 5'-nuclease assays using fluorescent dye-labeled allele-specific probes.
Genotype distribution did not deviate from the Hardy-Weinberg equilibrium. In the first group, patients homozygous for the variant allele T were found to be younger than C allele carriers (39.6 +/- 12.5 vs 45.7 +/- 11.5, P = 0.008). Among the histological lesions studied, portal lymphoid aggregates were more frequently observed among TT homozygotes than among C carriers (21/37 vs 32/100, P = 0.008). The presence of portal lymphoid aggregates was closely correlated with hepatic inflammation (P = 0.003) and with bile duct damage (P < 0.001). The degree of fibrosis, in contrast, was not found to be related to the CD14 gene C-159T polymorphism.
The data suggest a possible relationship between CD14 C-159T polymorphism and the formation of portal lymphoid aggregates, but not liver fibrosis progression in chronic hepatitis C.
分析CD14 rs2569190/C-159T单核苷酸多态性(SNP)与慢性丙型肝炎疾病进展之间的相关性。
分别对总共137例和349例慢性丙型肝炎患者的肝活检标本进行坏死性炎症活动(分级)和结构改变(分期)评估。在一组患者中,还研究了丙型肝炎特有的进一步组织学病变、丙型肝炎病毒亚型以及肝病的生化参数。使用荧光染料标记的等位基因特异性探针,通过5'-核酸酶测定法对基因组DNA样本进行相应SNP的基因分型。
基因型分布未偏离哈迪-温伯格平衡。在第一组中,发现变异等位基因T的纯合患者比C等位基因携带者更年轻(39.6±12.5对45.7±11.5,P = 0.008)。在所研究的组织学病变中,TT纯合子中门静脉淋巴滤泡的观察频率高于C等位基因携带者(21/37对32/100,P = 0.008)。门静脉淋巴滤泡的存在与肝脏炎症密切相关(P = 0.003),也与胆管损伤密切相关(P < 0.001)。相比之下,纤维化程度与CD14基因C-159T多态性无关。
数据表明CD14 C-159T多态性与门静脉淋巴滤泡的形成之间可能存在关联,但与慢性丙型肝炎的肝纤维化进展无关。