Laboratory of Photobiology and Molecular Diagnostics, Intercollegiate Faculty of Biotechnology University of Gdansk and Medical University of Gdansk, 80-307 Gdansk, Poland.
Division of Tropical Medicine and Epidemiology, Faculty of Health Sciences, Institute of Maritime and Tropical Medicine, Medical University of Gdansk, 81-519 Gdynia, Poland.
Viruses. 2023 Aug 9;15(8):1710. doi: 10.3390/v15081710.
Dysregulation of iron metabolism in chronic hepatitis C (CHC) is a significant risk factor for hepatic cirrhosis and cancer. We studied if known genetic variants related to iron homeostasis associate with liver disease progression in CHC. Retrospective analysis included 249 CHC patients qualified for antiviral therapy between 2004 and 2014. For all patients, nine SNPs within , , , , , , and genes were genotyped. Expression of selected iron-related genes, was determined with qRT-PCR in 124 liver biopsies, and mRNA expression of co-inhibitory receptors (, , ) was measured in 79 liver samples. rs884409, rs368328, rs7385804, and rs855791 associated with histopathological changes in liver tissue at baseline. The combination of minor allele in rs976552 and rs884409 linked with higher prevalence of hepatocellular carcinoma (HCC) during follow up (OR 8.1 CI 2.2-29.2; = 0.001). Minor allele in rs976552 associated with lower hepatic expression of . Tested polymorphisms related to iron homeostasis associate with histopathological changes in the liver. The presence of both rs976552 G and rs884409 G alleles correlates with HCC occurrence, especially in the group of patients with elevated AST (>129 IU/L). rs976552 in could impact immunological processes associated with carcinogenesis in CHC.
慢性丙型肝炎（CHC）中铁代谢失调是肝硬化和肝癌的重要危险因素。我们研究了与铁稳态相关的已知遗传变异是否与 CHC 中的肝脏疾病进展相关。回顾性分析包括 2004 年至 2014 年间符合抗病毒治疗条件的 249 例 CHC 患者。对所有患者进行了 、 、 、 、 、 基因内的 9 个 SNP 基因分型。在 124 例肝活检标本中用 qRT-PCR 测定了选定的铁相关基因 的表达，并在 79 个肝样本中测定了共抑制受体（ 、 、 ）的 mRNA 表达。 rs884409、rs368328、rs7385804 和 rs855791 与基线时肝组织的组织病理学变化相关。rs976552 和 rs884409 中的次要等位基因的组合与随访期间肝细胞癌（HCC）的更高患病率相关（OR 8.1 CI 2.2-29.2； = 0.001）。rs976552 中的次要等位基因与 的肝表达降低相关。测试的与铁稳态相关的多态性与肝脏的组织病理学变化相关。rs976552 中的 rs976552 G 和 rs884409 G 等位基因的存在与 HCC 的发生相关，尤其是在 AST 升高（>129 IU/L）的患者组中。 中的 rs976552 可能影响与 CHC 中癌变相关的免疫过程。
