Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2017 May;17(2):225-232.
doi: 10.1007/s10238-016-0423-4. Epub 2016 Apr 28.

Interferon lambda polymorphisms associate with body iron indices and hepatic expression of interferon-responsive long non-coding RNA in chronic hepatitis C

Anna Wróblewska  1 , Agnieszka Bernat  1 , Anna Woziwodzka  1 , Joanna Markiewicz  2 , Tomasz Romanowski  1 , Krzysztof P Bielawski  1 , Tomasz Smiatacz  3 , Katarzyna Sikorska  4   5
Affiliations

Interferon lambda polymorphisms associate with body iron indices and hepatic expression of interferon-responsive long non-coding RNA in chronic hepatitis C

Anna Wróblewska et al. Clin Exp Med. 2017 May.

Abstract

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.

Keywords: Hepatitis C, chronic; Interferon lambda; Iron overload; Polymorphism, single nucleotide; RNA, long non-coding.

PubMed Disclaimer

Conflict of interest statement

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

The study protocol was approved by the Local Independent Bioethics Committee at the Medical University of Gdansk (NKEB 246/2011) in compliance with the Declaration of Helsinki.

Informed consent

All enrolled participants of this study provided written informed consent.

Figures

Fig. 1
Fig. 1
Association of rs12979860 with biochemical parameters. Serum iron (a), ferritin (b), GGT (c) and HCV load (d) were measured in samples from CHC patients. For serum iron, ferritin and GGT n(CC) = 50, n(CT) = 103, n(TT) = 39; for viral load n(CC) = 24, n(CT) = 43, n(TT) = 16. Each dot represents a data point for one patient
Fig. 2
Fig. 2
Association of rs12979860 with hepatic gene expression. Expression of HAMP (a), NRIR (b) and RSAD2 (c) was measured in 105 liver biopsy samples of CHC patients; n(CC) = 26, n(CT) = 61 and n(TT) = 18. Each dot represents a data point for one patient
See this image and copyright information in PMC

References

    1. Wedemeyer H, Duberg AS, Buti M, et al. Strategies to manage hepatitis C virus (HCV) disease burden. J Viral Hepat. 2014;21(Suppl 1):60–89. doi: 10.1111/jvh.12249. - DOI - PubMed
    1. Ge D, Fellay J, Thompson AJ, et al. Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance. Nature. 2009;461(7262):399–401. doi: 10.1038/nature08309. - DOI - PubMed
    1. Suppiah V, Moldovan M, Ahlenstiel G, et al. IL28B is associated with response to chronic hepatitis C interferon-alpha and ribavirin therapy. Nat Genet. 2009;41(10):1100–1104. doi: 10.1038/ng.447. - DOI - PubMed
    1. Tanaka Y, Nishida N, Sugiyama M, et al. Genome-wide association of IL28B with response to pegylated interferon-alpha and ribavirin therapy for chronic hepatitis C. Nat Genet. 2009;41(10):1105–1109. doi: 10.1038/ng.449. - DOI - PubMed
    1. Urban TJ, Thompson AJ, Bradrick SS, et al. IL28B genotype is associated with differential expression of intrahepatic interferon-stimulated genes in patients with chronic hepatitis C. Hepatology. 2010;52(6):1888–1896. doi: 10.1002/hep.23912. - DOI - PMC - PubMed

LinkOut - more resources