Single nucleotide polymorphisms (SNPs) within DNA region containing interferon lambda 3 (IFNL3) and IFNL4 genes are prognostic factors of treatment response in chronic hepatitis C (CHC). Iron overload, frequently diagnosed in CHC, is associated with unfavorable disease course and a risk of carcinogenesis. Its etiology and relationship with the immune response in CHC are not fully explained. Our aim was to determine whether IFNL polymorphisms in CHC patients associate with body iron indices, and whether they are linked with hepatic expression of genes involved in iron homeostasis and IFN signaling. For 192 CHC patients, four SNPs within IFNL3-IFNL4 region (rs12979860, rs368234815, rs8099917, rs12980275) were genotyped. In 185 liver biopsies, histopathological analyses were performed. Expression of five mRNAs and three long non-coding RNAs (lncRNAs) was determined with qRT-PCR in 105 liver samples. Rs12979860 TT or rs8099917 GG genotypes as well as markers of serum and hepatocyte iron overload associated with higher activity of gamma-glutamyl transpeptidase and liver steatosis. The presence of two minor alleles in any of the tested SNPs predisposed to abnormally high serum iron concentration and correlated with higher hepatic expression of lncRNA NRIR. On the other hand, homozygosity in any major allele associated with higher viral load. Patients bearing rs12979860 CC genotype had lower hepatic expression of hepcidin (HAMP; P = 0.03). HAMP mRNA level positively correlated with serum iron indices and degree of hepatocyte iron deposits. IFNL polymorphisms influence regulatory pathways of cellular response to IFN and affect body iron balance in chronic hepatitis C virus infection.
Supplementary material 1 (DOCX 125 kb)10238_2016_423_MOESM1_ESM.docx
Sikorska K, Stalke P, Izycka-Swieszewska E, Romanowski T, Bielawski KP. The role of iron overload and HFE gene mutations in the era of pegylated interferon and ribavirin treatment of chronic hepatitis C. Med Sci Monit. 2010;16(3):CR137–43. PubMed
Barriocanal M, Carnero E, Segura V, Fortes P. Long non-coding RNA BST2/BISPR is induced by IFN and regulates the expression of the antiviral factor tetherin. Front Immunol. 2014;5:655. PubMed
Beaton MD, Adams PC. Treatment of hyperferritinemia. Ann Hepatol. 2012;11(3):294–300. PubMed
Sikorska K, Bielawski KP, Stalke P, et al. HFE gene mutations in Polish patients with disturbances of iron metabolism: an initial assessment. Int J Mol Med. 2005;16(6):1151–6. PubMed
Gaunt TR, Rodriguez S, Zapata C, Day IN. MIDAS: software for analysis and visualisation of interallelic disequilibrium between multiallelic markers. BMC Bioinform. 2006;7:227. CrossRef
Cherayil BJ. Iron and immunity: immunological consequences of iron deficiency and overload. Arch Immunol Ther Exp (Warsz). 2010;58(6):407–15. CrossRef
Ezoe S, Yokota T, Ishibashi T, Oritani K, Kanakura Y. Iron overload effects on immune system through the cytokine secretion by macrophage. Blood. 2013;122(21):1047.
Kambara H, Gunawardane L, Zebrowski E, et al. Regulation of Interferon-Stimulated Gene BST2 by a lncRNA Transcribed from a Shared Bidirectional Promoter. Front Immunol. 2014;5:676. PubMed
- Interferon lambda polymorphisms associate with body iron indices and hepatic expression of interferon-responsive long non-coding RNA in chronic hepatitis C
Krzysztof P. Bielawski
- Springer International Publishing
Neu im Fachgebiet Innere Medizin
Meistgelesene Bücher aus der Inneren Medizin
Mail Icon II