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Open Access 01-12-2017 | Research article

Genetic variation in the microsomal triglyceride transfer protein (−493G/T) is associated with hepatic steatosis in patients infected with hepatitis C virus

Authors: Mariana Cavalheiro Magri, Thamiris Vaz Gago Prata, Caroline Manchiero, Bianca Peixoto Dantas, Celso Carmo Mazza, Fátima Mitiko Tengan

Published in: BMC Infectious Diseases | Issue 1/2017

Abstract

Background

In chronic hepatitis C, the fibrosis progression rates are extremely variable and can be influenced by factors associated with the host, virus and environment. Among the associated metabolic factors, hepatic steatosis is characterized by an accumulation of triglycerides in hepatocytes. In the host, genetic determinants of hepatic steatosis are observed, such as single-nucleotide polymorphisms (SNPs) in the microsomal triglyceride transfer protein (MTTP) gene. The MTTP -493G/T SNP appears to play an important role in the regulation of gene expression and influences the plasma concentration of circulating low-density lipoprotein (LDL). The present study investigated the influence of this SNP in the development of hepatic steatosis in patients with chronic hepatitis C and evaluated the association of hepatic steatosis with certain characteristics of these patients and the hepatitis C virus (HCV).

Methods

Two hundred thirty-nine patients with chronic hepatitis C were genotyped for the MTTP -493G⁄T SNP by a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. The association between hepatic steatosis and selected characteristics of the patient and virus was evaluated using bivariate and multivariate analyses.

Results

The most prevalent MTTP -493G/T genotype was GG (46%) followed by GT (43.5%) and TT (10.5%). Multivariate analysis of the total cohort revealed associations between the presence of hepatic steatosis and inflammatory activity of moderate to high intensity (P < 0.001), advanced age (P = 0.010), elevated gamma glutamyl transpeptidase (GGT) levels (P = 0.010) and low LDL levels (P = 0.022). Hepatic steatosis was also associated with the TT/GT genotype of the MTTP -493G⁄T SNP in patients infected with HCV genotype 3 (P < 0.001).

Conclusions

In chronic hepatitis C patients infected with HCV genotype 3 and with the TT/GT genotype of the MTTP -493G/T SNP, a significant increase in hepatic steatosis was observed, which may indicate that this SNP has a significant influence on the accumulation of triglycerides in hepatocytes. Furthermore, associations were observed between hepatic steatosis and inflammatory activity of moderate to high intensity, advanced age, elevated GGT and low LDL levels.

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Title: Genetic variation in the microsomal triglyceride transfer protein (−493G/T) is associated with hepatic steatosis in patients infected with hepatitis C virus
Authors: Mariana Cavalheiro Magri
Thamiris Vaz Gago Prata
Caroline Manchiero
Bianca Peixoto Dantas
Celso Carmo Mazza
Fátima Mitiko Tengan
Publication date: 01-12-2017
Publisher: BioMed Central
Published in: BMC Infectious Diseases / Issue 1/2017
Electronic ISSN: 1471-2334
DOI: https://doi.org/10.1186/s12879-017-2340-x

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Genetic variation in the microsomal triglyceride transfer protein (−493G/T) is associated with hepatic steatosis in patients infected with hepatitis C virus

Abstract

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Methods

Results

Conclusions

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