Genetic polymorphisms of interleukin-6 modulate fibrosis progression in mild chronic hepatitis C

Abstract Genetic polymorphisms of interleukin-6 (IL-6) (-1363G>T, -597G>A, -572G>C, -174G>C, +2954G>C) may affect the outcomes of several diseases. This study was aimed to verify the role of these polymorphisms on the disease progression of patients with hepatitis C virus (HCV) infect...

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Published in:Human immunology 2010-10, Vol.71 (10), p.999-1004
Main Authors: Falleti, Edmondo, Fabris, Carlo, Vandelli, Carmen, Colletta, Cosimo, Cussigh, Annarosa, Smirne, Carlo, Fontanini, Elisabetta, Cmet, Sara, Minisini, Rosalba, Bitetto, Davide, Toniutto, Pierluigi, Pirisi, Mario
Format: Article
Language:English
Subjects:
Adolescent
Adult
Allergy and Immunology
Biopsy
Child
Disease Progression
Female
Follow-Up Studies
Gene Frequency
Genotype
Hepatitis C
Hepatitis C virus
Hepatitis C, Chronic - genetics
Hepatitis C, Chronic - immunology
Hepatitis C, Chronic - physiopathology
Humans
Interleukin-6
Interleukin-6 - genetics
Liver Cirrhosis
Male
Middle Aged
Normal alanine aminotransferase
Polymorphism, Genetic
Polymorphisms
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Summary:Abstract Genetic polymorphisms of interleukin-6 (IL-6) (-1363G>T, -597G>A, -572G>C, -174G>C, +2954G>C) may affect the outcomes of several diseases. This study was aimed to verify the role of these polymorphisms on the disease progression of patients with hepatitis C virus (HCV) infection and persistently normal transaminases (PNALT). A total of 121 PNALT patients did not receive any antiviral treatment but underwent periodic clinical monitoring, including repeat biopsies, for a median of 120 months. IL6-1363G>T, -597G>A, -572G>C, -174G>C, +2954G>C polymorphisms were related to histologic fibrosis progression. Among patients whose grading and staging scores increased at the end of the follow-up ≥2 Ishak points ( N = 60 and N = 26, respectively), IL-6 -174G>C genotype frequencies were GG 37/66, GC 21/45, CC 2/10 ( p = 0.041) and GG 18/66, GC 8/45, CC 0/10 ( p = 0.040), respectively. The following frequencies were observed for the 572G>C polymorphism: GG 50/105, GC 10/16, CC 0/0, and GG 19/105, GC 7/16, CC 0/0, respectively. Grading progression was independently associated with carriage of the G allele in -174G>C polymorphism (oddd ratio = 5.07%, 95% confidence interval = 0.959–26.8, p = 0.023). Staging progression was independently associated with carriage of the C allele in -572G>C polymorphism (odd ratio = 4.60%, 95% confidence interval 1.42–14.8, p = 0.012). IL-6 polymorphisms influence histologic progression of HCV in patients with PNALT.
ISSN:0198-8859
1879-1166
DOI:10.1016/j.humimm.2010.06.006