Microsomal triglyceride transfer protein polymorphism (-493G/T) is associated with hepatic steatosis in patients with chronic hepatitis C.
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.
Mirandola
Silvia
S
Venetian Institute of Molecular Medicine, Padova, Italy.
Osterreicher
Christoph H
CH
Marcolongo
Moira
M
Datz
Christian
C
Aigner
Elmar
E
Schlabrakowski
Anne
A
Realdon
Stefano
S
Gerotto
Martina
M
Alberti
Alfredo
A
Stickel
Felix
F
D000328:Adult; D016632:Apolipoprotein A-I / Q000097:blood; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D018450:Disease Progression; D005234:Fatty Liver / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D019698:Hepatitis C, Chronic / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008075:Lipoproteins, HDL / Q000097:blood; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D012307:Risk Factors
D016632:Apolipoprotein A-I; D002352:Carrier Proteins; D008075:Lipoproteins, HDL; D012333:RNA, Messenger; C106092:microsomal triglyceride transfer protein