Rudnicka Alina, Woziwodzka Anna, Wróblewska Anna, Rybicka Magda, Bielawski Krzysztof P, Sikorska Katarzyna, Bernat Agnieszka
Department of Molecular Diagnostics, Intercollegiate Faculty of Biotechnology, University of Gdansk-Medical University of Gdansk, Gdansk, Poland.
Department of Tropical Medicine and Epidemiology, Medical University of Gdansk, Gdynia, Poland.
J Gastroenterol Hepatol. 2017 Feb;32(2):482-486. doi: 10.1111/jgh.13495.
Pathological iron overload is commonly found in chronic hepatitis C (CHC) patients and considered as a negative prognostic factor of the disease. A single nucleotide polymorphism (SNP) rs884409 in duodenal cytochrome b gene (CYBRD1) is implicated in the pathogenesis of hemochromatosis. In our study we investigated the impact of the CYBRD1 genotype and expression on iron overload in CHC patients.
Liver biopsy specimens and whole blood samples from 243 patients with CHC were included in the study. Iron deposits in hepatocytes, serum markers of iron overload, and expression profile of gene-regulators of iron homeostasis were analyzed. Genotyping and analysis of gene expression of the CYBRD1 were performed. The frequency of SNP and the expression levels of CYBRD1 were compared between the groups of patients with and without markers of iron overload.
The single nucleotide variant rs884409 G was associated with elevated serum iron levels, increased markers of liver inflammation, and oxidative stress. Hepatic expression of CYBRD1 was associated with the expression of Tfr2, Id1, and HO-1 genes, serum ferritin levels, and with increased iron accumulation in liver.
These results implicate CYBRD1 involvement in iron homeostasis in CHC.
病理性铁过载在慢性丙型肝炎（CHC）患者中普遍存在，并被视为该疾病的不良预后因素。十二指肠细胞色素b基因（CYBRD1）中的单核苷酸多态性（SNP）rs884409与血色素沉着症的发病机制有关。在我们的研究中，我们调查了CYBRD1基因型和表达对CHC患者铁过载的影响。
本研究纳入了243例CHC患者的肝活检标本和全血样本。分析了肝细胞中的铁沉积、铁过载的血清标志物以及铁稳态基因调节因子的表达谱。对CYBRD1进行基因分型和基因表达分析。比较了有和没有铁过载标志物的患者组之间SNP的频率和CYBRD1的表达水平。
单核苷酸变异rs884409 G与血清铁水平升高、肝脏炎症标志物增加和氧化应激有关。CYBRD1的肝脏表达与Tfr2、Id1和HO-1基因的表达、血清铁蛋白水平以及肝脏中铁积累增加有关。
这些结果表明CYBRD1参与了CHC中的铁稳态。
