Journal
JOURNAL OF HEPATOLOGY
Volume 55, Issue 3, Pages 529-535Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jhep.2010.12.020
Keywords
Hepatitis C; Steatosis; Genome-wide association study
Categories
Funding
- Swiss National Science Foundation [3347C0-108782/1, 314730-130498]
- Swiss Federal Office for Education and Sciences [03.0599]
- European Commission [LSHM-CT-2004-503359]
- Swiss School of Public Health Plus
- Swiss National Foundation [32003B-127613]
- Leenaards foundation
- Swiss National Science Foundation (SNF) [32003B_127613] Funding Source: Swiss National Science Foundation (SNF)
Ask authors/readers for more resources
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 1148 M 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-gamma (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% Cl = 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. (C) 2011 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available