Microsomal triglyceride transfer protein polymorphism (-493G/T) is associated with hepatic steatosis in patients with chronic hepatitis C

Silvia Mirandola, Christoph H. Österreicher, Moira Marcolongo, Christian Datz, Elmar Aigner, Anne Schlabrakowski, Stefano Realdon, Martina Gerotto, Alfredo Alberti, Felix Stickel

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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 ± 0.3g/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.

Original languageEnglish
Pages (from-to)557-565
Number of pages9
JournalLiver International
Volume29
Issue number4
DOIs
Publication statusPublished - 2009

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Chronic Hepatitis C
Hepacivirus
Liver
Alleles
Body Mass Index
Fats
Odds Ratio
Genotype
Confidence Intervals
microsomal triglyceride transfer protein
Messenger RNA
Apolipoprotein A-I
Apolipoproteins B
HDL Lipoproteins
Lipoproteins
Fibrosis

Keywords

  • Genetic risk
  • Hepatitis C
  • Lipid metabolism
  • Metabolic syndrome
  • Microsomal triglyceride transfer protein
  • Steatosis

ASJC Scopus subject areas

  • Hepatology

Cite this

Mirandola, S., Österreicher, C. H., Marcolongo, M., Datz, C., Aigner, E., Schlabrakowski, A., ... Stickel, F. (2009). Microsomal triglyceride transfer protein polymorphism (-493G/T) is associated with hepatic steatosis in patients with chronic hepatitis C. Liver International, 29(4), 557-565. https://doi.org/10.1111/j.1478-3231.2008.01892.x

Microsomal triglyceride transfer protein polymorphism (-493G/T) is associated with hepatic steatosis in patients with chronic hepatitis C. / Mirandola, Silvia; Österreicher, Christoph H.; Marcolongo, Moira; Datz, Christian; Aigner, Elmar; Schlabrakowski, Anne; Realdon, Stefano; Gerotto, Martina; Alberti, Alfredo; Stickel, Felix.

In: Liver International, Vol. 29, No. 4, 2009, p. 557-565.

Research output: Contribution to journalArticle

Mirandola, S, Österreicher, CH, Marcolongo, M, Datz, C, Aigner, E, Schlabrakowski, A, Realdon, S, Gerotto, M, Alberti, A & Stickel, F 2009, 'Microsomal triglyceride transfer protein polymorphism (-493G/T) is associated with hepatic steatosis in patients with chronic hepatitis C', Liver International, vol. 29, no. 4, pp. 557-565. https://doi.org/10.1111/j.1478-3231.2008.01892.x
Mirandola, Silvia ; Österreicher, Christoph H. ; Marcolongo, Moira ; Datz, Christian ; Aigner, Elmar ; Schlabrakowski, Anne ; Realdon, Stefano ; Gerotto, Martina ; Alberti, Alfredo ; Stickel, Felix. / Microsomal triglyceride transfer protein polymorphism (-493G/T) is associated with hepatic steatosis in patients with chronic hepatitis C. In: Liver International. 2009 ; Vol. 29, No. 4. pp. 557-565.
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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 ± 0.3g/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.",
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T1 - Microsomal triglyceride transfer protein polymorphism (-493G/T) is associated with hepatic steatosis in patients with chronic hepatitis C

AU - Mirandola, Silvia

AU - Österreicher, Christoph H.

AU - Marcolongo, Moira

AU - Datz, Christian

AU - Aigner, Elmar

AU - Schlabrakowski, Anne

AU - Realdon, Stefano

AU - Gerotto, Martina

AU - Alberti, Alfredo

AU - Stickel, Felix

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N2 - 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 ± 0.3g/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.

AB - 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 ± 0.3g/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.

KW - Genetic risk

KW - Hepatitis C

KW - Lipid metabolism

KW - Metabolic syndrome

KW - Microsomal triglyceride transfer protein

KW - Steatosis

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