Tao Cai1, Jean-François Dufour2, Beat Muellhaupt3, Tilman Gerlach4, Markus Heim5, Darius Moradpour6, Andreas Cerny7, Raffaele Malinverni8, Vincent Kaddai9, Murielle Bochud10, Francesco Negro11, Pierre-Yves Bochud1. 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.
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) infectedpatients. 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.
Authors: Samir R Shah; Keyur Patel; Patrick Marcellin; Graham R Foster; Michael Manns; Shyam Kottilil; Letha Healey; Erik Pulkstenis; G Mani Subramanian; John G McHutchison; Mark S Sulkowski; Stefan Zeuzem; David R Nelson Journal: Clin Gastroenterol Hepatol Date: 2011-05-13 Impact factor: 11.382
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Authors: Etienne Patin; Zoltán Kutalik; Julien Guergnon; Stéphanie Bibert; Bertrand Nalpas; Emmanuelle Jouanguy; Mona Munteanu; Laurence Bousquet; Laurent Argiro; Philippe Halfon; Anne Boland; Beat Müllhaupt; David Semela; Jean-François Dufour; Markus H Heim; Darius Moradpour; Andreas Cerny; Raffaele Malinverni; Hans Hirsch; Gladys Martinetti; Vijayaprakash Suppiah; Graeme Stewart; David R Booth; Jacob George; Jean-Laurent Casanova; Christian Bréchot; Charles M Rice; Andrew H Talal; Ira M Jacobson; Marc Bourlière; Ioannis Theodorou; Thierry Poynard; Francesco Negro; Stanislas Pol; Pierre-Yves Bochud; Laurent Abel Journal: Gastroenterology Date: 2012-07-27 Impact factor: 22.682