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World J Gastroenterol. Apr 28, 2013; 19(16): 2449-2455
Published online Apr 28, 2013. doi: 10.3748/wjg.v19.i16.2449
Genetic association of interleukin-6 polymorphism (-174 G/C) with chronic liver diseases and hepatocellular carcinoma
Lydia Giannitrapani, Maurizio Soresi, Daniele Balasus, Anna Licata, Giuseppe Montalto
Lydia Giannitrapani, Maurizio Soresi, Daniele Balasus, Anna Licata, Giuseppe Montalto, Unit of Internal Medicine, Biomedical Department of Internal Medicine and Specialties DiBiMIS, University of Palermo, 90127 Palermo, Italy
Author contributions: Giannitrapani L and Soresi M collected and analyzed literature data; Balasus D and Licata A contributed analytic tools; Montalto G supervised the paper and Giannitrapani L wrote the paper.
Correspondence to: Dr. Lydia Giannitrapani, Unit of Internal Medicine, Biomedical Department of Internal Medicine and Specialties, University of Palermo, Via del Vespro 141, 90127 Palermo, Italy. lydia.giannitrapani@unipa.it
Telephone: +39-91-6552916 Fax: +39-91-6552977
Received: December 16, 2012
Revised: March 6, 2013
Accepted: March 22, 2013
Published online: April 28, 2013
Abstract

Interleukin-6 (IL-6) is a pleiotropic cytokine which is expressed in many inflammatory cells in response to different types of stimuli, regulating a number of biological processes. The IL-6 gene is polymorphic in both the 5’ and 3’ flanking regions and more than 150 single nucleotide polymorphisms have been identified so far. Genetic polymorphisms of IL-6 may affect the outcomes of several diseases, where the presence of high levels of circulating IL-6 have been correlated to the stage and/or the progression of the disease itself. The -174 G/C polymorphism is a frequent polymorphism, that is located in the upstream regulatory region of the IL-6 gene and affects IL-6 production. However, the data in the literature on the genetic association between the -174 G/C polymorphism and some specific liver diseases characterized by different etiologies are still controversial. In particular, most of the studies are quite unanimous in describing a correlation between the presence of the high-producer genotype and a worse evolution of the chronic liver disease. This is valid for patients with hepatitis C virus (HCV)-related chronic hepatitis and liver cirrhosis and hepatocellular carcinoma (HCC) whatever the etiology. Studies in hepatitis B virus-related chronic liver diseases are not conclusive, while specific populations like non alcoholic fatty liver disease/non-alcoholic steatohepatitis, autoimmune and human immunodeficiency virus/HCV co-infected patients show a higher prevalence of the low-producer genotype, probably due to the complexity of these clinical pictures. In this direction, a systematic revision of these data should shed more light on the role of this polymorphism in chronic liver diseases and HCC.

Keywords: Single nucleotide polymorphisms, Interleukin-6, Chronic hepatitis, Liver cirrhosis, Hepatocellular carcinoma

Core tip: Several studies suggested the possibility of an association between -174 interleukin-6 gene G/C polymorphism and some liver diseases however, the data in the literature are still controversial. This work aims to review the literature data on the role of this polymorphism and its possible biological function in chronic liver diseases and hepatocellular carcinoma.