Abstract
The reduction of hepatic microsomal transfer protein (MTP) activity results in fatty liver, worsening hepatic steatosis and fibrosis in chronic hepatitis C (CHC). The G allele of the MTP gene promoter, -493G/T, has been associated with lower transcriptional activity than the T allele. We investigated this association with metabolic and histological variables in patients with CHC. A total of 174 untreated patients with CHC were genotyped for MTP -493G/T by direct sequencing using PCR. All patients were negative for markers of Wilson's disease, hemochromatosis and autoimmune diseases and had current and past daily alcohol intake lower than 100 g/week. The sample distribution was in Hardy-Weinberg equilibrium. Among subjects with genotype 1, 56.8% of the patients with fibrosis grade 3+4 presented at least one G allele versus 34.3% of the patients with fibrosis grade 1+2 (OR = 1.8; 95%CI = 1.3-2.3). Logistic regression analysis with steatosis as the dependent variable identified genotypes GG+GT as independent protective factors against steatosis (OR = 0.4, 95%CI = 0.2-0.8; P = 0.01). The results suggest that the presence of the G allele of MTP -493G/T associated with lower hepatic MTP expression protects against steatosis in our CHC patients.
Highlights
Hepatitis C virus (HCV) infects about 2-3% of the world population [1], leading to chronic hepatitis in up to 60-80% of infected individuals and is associated with liver steatosis, fibrosis and insulin resistance [2,3].Chronic hepatitis C (CHC) is characterized by inflammatory lesions in the liver and is recognized as a systemic disease involving lipid metabolism, oxidative stress and mitochondrial function [4,5]
We set out to establish the role of the genetic microsomal transfer protein (MTP) -493G/T single nucleotide polymorphism (SNP) in the pathogenesis of steatosis and Genotype non-1
Our data showed that the G allele was more frequently present in CHC patients infected with genotype 1 with higher degrees of fibrosis
Summary
Hepatitis C virus (HCV) infects about 2-3% of the world population [1], leading to chronic hepatitis in up to 60-80% of infected individuals and is associated with liver steatosis, fibrosis and insulin resistance [2,3].Chronic hepatitis C (CHC) is characterized by inflammatory lesions in the liver and is recognized as a systemic disease involving lipid metabolism, oxidative stress and mitochondrial function [4,5]. The onset and progression of fibrosis are the direct result of local inflammation that triggers stellate cell activation [6]. Both host and viral factors are implicated in the development of HCV-associated steatosis, but their contribution varies widely as a function of viral genotype. This is supported by the observation that the degree of liver steatosis is directly related to the level of HCV replication as measured by serum HCV-RNA, at least in patients infected with HCV genotype 3, in the absence of confounding metabolic causes of steatosis [type 2 diabetes, obesity or increased body mass index (BMI)] [7,8]. There is strong evidence suggesting that some HCV proteins, the structural capsid protein, core, and the non-structural protein, NS5A, can induce hepatic steatosis [9,10]
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