Department of Internal Medicine I, University of Bonn, Germany.
Department of Internal Medicine I, University of Bonn, Germany; German Center for Infection Research, Germany.
J Hepatol. 2014 Nov;61(5):1073-9. doi: 10.1016/j.jhep.2014.06.006. Epub 2014 Jun 16.
BACKGROUND & AIMS: The genetic background of alcoholic liver diseases and their complications are increasingly recognized. A common polymorphism in the neurocan (NCAN) gene, which is known to be expressed in neuronal tissue, has been identified as a risk factor for non-alcoholic fatty liver disease (NAFLD). We investigated if this polymorphism may also be related to alcoholic liver disease (ALD) and hepatocellular carcinoma (HCC).
We analysed the distribution of the NCAN rs2228603 genotypes in 356 patients with alcoholic liver cirrhosis, 126 patients with alcoholic HCC, 382 persons with alcohol abuse without liver damage, 362 healthy controls and in 171 patients with hepatitis C virus (HCV) associated HCC. Furthermore, a validation cohort of 229 patients with alcoholic cirrhosis (83 with HCC) was analysed. The genotypes were determined by LightSNiP assays. The expression of NCAN was studied by RT-PCR and immunofluorescence microscopy.
The frequency of the NCAN rs2228603 T allele was significantly increased in patients with HCC due to ALD (15.1%) compared to alcoholic cirrhosis without HCC (9.3%), alcoholic controls (7.2%), healthy controls (7.9%), and HCV associated HCC (9.1%). This finding was confirmed in the validation cohort (15.7% vs. 6.8%, OR=2.53; 95%CI: 1.36-4.68; p=0.0025) and by multivariate analysis (OR=1.840; 95%CI: 1.22-2.78; p=0.004 for carriage of the rs2228603 T allele). In addition, we identified and localised NCAN expression in human liver.
NCAN is not only expressed in neuronal tissue, but also in the liver. Its rs2228603 polymorphism is a risk factor for HCC in ALD, but not in HCV infection.
酒精性肝病及其并发症的遗传背景日益受到重视。神经钙黏蛋白（NCAN）基因的一个常见多态性，已知在神经元组织中表达，已被确定为非酒精性脂肪性肝病（NAFLD）的危险因素。我们研究了这种多态性是否也与酒精性肝病（ALD）和肝细胞癌（HCC）有关。
我们分析了 356 例酒精性肝硬化患者、126 例酒精性 HCC 患者、382 例酒精滥用无肝损伤患者、362 例健康对照者和 171 例丙型肝炎病毒（HCV）相关 HCC 患者中 NCAN rs2228603 基因型的分布。此外，还分析了 229 例酒精性肝硬化患者（83 例 HCC）的验证队列。通过 LightSNiP 测定法确定基因型。通过 RT-PCR 和免疫荧光显微镜研究 NCAN 的表达。
与无 HCC 的酒精性肝硬化（9.3%）、酒精性对照组（7.2%）、健康对照组（7.9%）和 HCV 相关 HCC（9.1%）相比，ALD 所致 HCC 患者中 NCAN rs2228603 T 等位基因的频率明显升高（15.1%）。这一发现在验证队列中得到了证实（15.7%比 6.8%，OR=2.53；95%CI：1.36-4.68；p=0.0025），并且通过多变量分析（OR=1.840；95%CI：1.22-2.78；p=0.004 携带 rs2228603 T 等位基因）。此外，我们还鉴定并定位了人类肝脏中的 NCAN 表达。
NCAN 不仅在神经元组织中表达，也在肝脏中表达。其 rs2228603 多态性是 ALD 中 HCC 的危险因素，但不是 HCV 感染的危险因素。
