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J Hepatol. 2011 Sep;55(3):529-535. doi: 10.1016/j.jhep.2010.12.020. Epub 2011 Jan 12.

Viral genotype-specific role of PNPLA3, PPARG, MTTP, and IL28B in hepatitis C virus-associated steatosis.

Author information

1
Infectious Diseases Service, Department of Medicine, University Hospital and University of Lausanne, Switzerland; Institute of Microbiology, University Hospital and University of Lausanne, Switzerland.
2
Division of Clinical Pharmacology, University Hospital, Bern, Switzerland.
3
Division of Gastroenterology and Hepatology, University Hospital, Zurich, Switzerland.
4
Division of Gastroenterology, Canton Hospital, St. Gallen, Switzerland.
5
Division of Gastroenterology and Hepatology, University Hospital, Basel, Switzerland.
6
Division of Gastroenterology and Hepatology, CHUV, Lausanne, Switzerland.
7
Clinica Moncucco, Lugano, Switzerland.
8
Pourtalès Hospital, Neuchâtel, Switzerland.
9
Division of Clinical Pathology, University Hospitals, Geneva, Switzerland.
10
Institute of Social and Preventive Medicine, CHUV, Lausanne, Switzerland.
11
Division of Clinical Pathology, University Hospitals, Geneva, Switzerland; Division of Gastroenterology and Hepatology, University Hospitals, Geneva, Switzerland. Electronic address: Francesco.Negro@hcuge.ch.

Abstract

BACKGROUND & AIMS:

Steatosis is a prominent feature of hepatitis C, especially in patients infected with genotype 3. The analysis of genetic polymorphisms influencing steatosis in chronic hepatitis C has been limited by the studies' small sample size, and important single nucleotide polymorphisms (SNPs), such as those in the patatin-like phospholipase family 3 protein (PNPLA3), were never evaluated.

METHODS:

We analyzed the role of SNPs, from 19 systematically selected candidate genes, on steatosis in 626 Caucasian hepatitis C virus (HCV) infected patients. SNPs were extracted from a genome-wide association-generated dataset. Associations of alleles with the presence and/or different severity of steatosis were evaluated by univariate and multivariate logistic regression, accounting for all relevant covariates.

RESULTS:

The risk of steatosis was increased by carriage of I148M in PNPLA3, but only in patients with HCV genotypes non-3 (odds ratio [OR]=1.9, 95% confidence interval [CI]=1.6-2.3, p<0.001) and similar, albeit weaker associations were found for SNPs in peroxisome proliferator-activated receptor-γ (PPARG) and interleukin-28B (IL28B). Carriage of a SNP in the microsomal triglyceride transfer protein (MTTP) increased the risk of steatosis, but only in patients with HCV genotype 3 (rs1800803, OR=3.4, 95% CI=2.4-4.9, p=0.001).

CONCLUSIONS:

The rs738409 SNP in PNPLA3 is associated with an increased risk of steatosis in patients infected with HCV genotypes non-3. Host genes affect steatosis depending on the infecting HCV genotype, suggesting their interaction with viral factors.

PMID:
21236304
DOI:
10.1016/j.jhep.2010.12.020
[Indexed for MEDLINE]
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