Microsomal triglyceride transfer protein (MTP) –493G/T gene polymorphism contributes to fat liver accumulation in HCV genotype 3 infected patients

Abstract

(A) A reduced activity of microsomal triglyceride transfer protein (MTP), a key enzyme of assembly/secretion of lipoproteins, is related to HCV steatosis. Host genetic background may influence development of steatosis. The aim of the study was to investigate the association between MTP-493 G/T gene polymorphism, fat liver accumulation and fibrosis progression in HCV infected patients. A total of 102 naïve patients with liver biopsy proven chronic hepatitis C were evaluated for MTP-493 G/T gene polymorphism, HCV RNA, HCV genotype, HOMA-IR, serum adiponectin, TNF-alpha and serum lipid levels. HCV genotype 3 infected patients carrying the T allele of the MTP gene polymorphism showed higher degree of steatosis than those carrying GG genotype (3.45 +/- 0.37 vs 1.30 +/- 0.45, respectively; P < 0.001). MTP'T' allele carriers also had higher HCV RNA serum levels (P < 0.01) and hepatic fibrosis (P < 0.001). Irrespective of MTP genotype, patients with HCV genotype 3 had lower levels of cholesterol, ApoB, HDL and LDL. In HCV genotype non-3 infected patients no parameters were associated with MTP gene polymorphism. In conclusion the presence of T allele of MTP-493G/T gene polymorphism predisposes patients infested with HCV genotype 3 to develop higher degree of fatty liver accumulation.

Genetic determinants of hepatic steatosis in man

“…However, in chronic HCV infection, the T allele is associated with decreased MTTP expression, which may occur either through a direct binding of some HCV proteins at the Ϫ 493 site or through an upregulation of MTTP-suppressor(s) by HCV ( 179 ). There is also an association between Ϫ 493T and hepatic steatosis in both HCV genotype 3-and nongenotype 3-infected patients ( 180,181 ). Increased lipid droplet accumulation in hepatocytes may provide a safe environment for HCV latency ( 179 ).…”

Dyslipoproteinemia in Chronic HCV Infection

“…Hypobetalipoproteinemia, reduced activity of MTP with negative correlation to hepatic steatosis and viral load, is observed in HCV-G3 chronic infection [11]. Secretion of apoB-100 was reduced by HCV nonstructural proteins using the HCV subgenomic replicon expression system and interaction between the HCV NS5A and apoB-100 was observed [12].…”

Evolving Trends in the Hepatitis C Virus Molecular Epidemiology Studies: From the Viral Sequences to the Human Genome

“…Zampino et al revealed that the presence of T allele in the −493G/T polymorphism of microsomal triglyceride transfer protein (MTP) gene reduces the activity of this key enzyme of assembly/secretion of lipoproteins and predisposes patients infected with HCV genotype 3 to develop higher degree of fatty liver accumulation [140]. Moreover, the SNP rs738409 of adiponutrin/patatin-like phospholipase domain-containing 3 (PNPLA3), which encodes for the I148M protein variant, has been recognized as a determinant of liver fat content.…”