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Microsomal triglyceride transfer protein polymorphism (−493G/T) is associated with hepatic steatosis in patients with chronic hepatitis C
Authors:Silvia Mirandola  Christoph H. Österreicher  Moira Marcolongo  Christian Datz  Elmar Aigner  Anne Schlabrakowski  Stefano Realdon  Martina Gerotto  Alfredo Alberti  Felix Stickel
Abstract:Background: Hepatic steatosis may promote progression of chronic hepatitis C (CHC). Microsomal triglyceride transfer protein (MTP) is required for assembly and secretion of ApoB lipoprotein and is implicated in hepatitis C virus (HCV)‐related steatosis. The MTP ?493G/T polymorphism may promote liver fat accumulation, but its role in HCV‐related steatosis is still unclear. Methods: Two hundred ninety‐eight CHC patients were studied and genotyped for MTP ?493G/T variants. Hepatic MTP mRNA expression and activity were determined in a subgroup. Results: Patients with grades 2/3 steatosis were older, had a higher body mass index (BMI), more advanced fibrosis and lower MTP mRNA expression and carried more often HCV genotype 3 and the MTP T allele. Age, BMI, HCV‐3 and MTP T allele [odds ratio (OR) 2.05; 95% confidence interval (CI) 1.2–3.53; P=0.009] were independent risk factors for steatosis grades 2/3, and in HCV genotype non‐3 patients, the MTP T allele was the strongest predictor for steatosis grade 2/3 (OR 2.17; 95% CI 1.22–3.86; P=0.008). Moreover, TT carriers had higher high‐density lipoprotein (65.6±14.6 vs 56.1±16.2 mg/dl; P=0.003) and apolipoprotein AI (1.80±0.3 vs 1.60±0.3 g/L; P=0.005) levels than G allele carriers. Conclusions: Chronic hepatitis C patients with the MTP ?493T allele reveal higher grades of steatosis, indicating a relevant contribution to liver fat accumulation, particularly in HCV non‐3 patients.
Keywords:genetic risk  hepatitis C  lipid metabolism  metabolic syndrome  microsomal triglyceride transfer protein  steatosis
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