TM6SF2 E167K variant is associated with severe steatosis in chronic hepatitis C, regardless of PNPLA3 polymorphism.

Abstract

BACKGROUND & AIMS:

A common non-synonymous polymorphism, E167K, in transmembrane six superfamily member 2 (TM6SF2) gene has been recently associated with an increased hepatic triglyceride content, dyslipidemia and liver fibrosis in NAFLD patients. We investigated possible associations between the TM6SF2 variants and liver lesions in chronic hepatitis C.

PATIENTS AND METHODS:

148 consecutive patients with biopsy proven anti-HCV/HCV-RNA-positive chronic hepatitis, naive for antiviral therapy, were genotyped for TM6SF2 E167K and PNPLA3 I148M variants.

RESULTS:

The score of liver steatosis was higher in the 18 patients with TM6SF2 E167K variant (mean 1.9 ± 1.3) than in the 130 homozygotes for TM6SF2 167E allele (1.1 ± 1.1, P = 0.02), and the prevalence of a steatosis score ≥ 3 was 33.3% vs. 12.3% respectively (P = 0.02). No difference in necroinflammatory or fibrosis scores was found between the two groups. A general linear model identified as independent predictors of steatosis TM6SF2 E167K and PNPLA3 M148M variants and waist circumference (P = 0.0376, P = 0.0069 and P = 0.0273 respectively).

CONCLUSIONS:

This is the first demonstration that TM6SF2 E167K variant is an independent predictor of liver steatosis in chronic hepatitis C.

• Authors: Nicola Coppola, Zampino Rosa, Grazia Cirillo, Maria Stanzione, Margherita Macera, Adriana Boemio, Anna Grandone, Mariantonietta Pisaturo, Aldo Marrone, Luigi E Adinolfi, Evangelista Sagnelli, Emanuele Miraglia del Giudice
• Journal: Liver international : official journal of the International Association for the Study of the Liver (Liver Int) Vol. 35 Issue 8 Pg. 1959-63 (Aug 2015) ISSN: 1478-3231 [Electronic] United States
• PMID: 25581573 (Publication Type: Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Chemical References

• Antiviral Agents
• Membrane Proteins
• TM6SF2 protein, human
• Lipase
• adiponutrin, human

Topics

• Adult
• Analysis of Variance
• Antiviral Agents (therapeutic use)
• Cohort Studies
• Female
• Genetic Predisposition to Disease (epidemiology)
• Genotype
• Hepatitis C, Chronic (complications, drug therapy, genetics)
• Humans
• Incidence
• Italy (epidemiology)
• Linear Models
• Lipase (genetics)
• Male
• Membrane Proteins (genetics)
• Middle Aged
• Non-alcoholic Fatty Liver Disease (epidemiology, etiology, genetics)
• Polymorphism, Single Nucleotide
• Prognosis
• Retrospective Studies
• Risk Assessment
• Severity of Illness Index