title: Viral genotype-specific role of PNPLA3, PPARG, MTTP, and IL28B in hepatitis C virus-associated steatosis.
abstract: OBJECTIVE
  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.
authors.affiliation: Infectious Diseases Service, Department of Medicine, University Hospital and University of Lausanne, Switzerland; Institute of Microbiology, University Hospital and University of Lausanne, Switzerland.
authors.forename: Tao
authors.initials: T
authors.lastname: Cai
authors.affiliation: Division of Clinical Pharmacology, University Hospital, Bern, Switzerland.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Dufour
authors.affiliation: Division of Gastroenterology and Hepatology, University Hospital, Zurich, Switzerland.
authors.forename: Beat
authors.initials: B
authors.lastname: Muellhaupt
authors.affiliation: Division of Gastroenterology, Canton Hospital, St. Gallen, Switzerland.
authors.forename: Tilman
authors.initials: T
authors.lastname: Gerlach
authors.affiliation: Division of Gastroenterology and Hepatology, University Hospital, Basel, Switzerland.
authors.forename: Markus
authors.initials: M
authors.lastname: Heim
authors.affiliation: Division of Gastroenterology and Hepatology, CHUV, Lausanne, Switzerland.
authors.forename: Darius
authors.initials: D
authors.lastname: Moradpour
authors.affiliation: Clinica Moncucco, Lugano, Switzerland.
authors.forename: Andreas
authors.initials: A
authors.lastname: Cerny
authors.affiliation: Pourtalès Hospital, Neuchâtel, Switzerland.
authors.forename: Raffaele
authors.initials: R
authors.lastname: Malinverni
authors.affiliation: Division of Clinical Pathology, University Hospitals, Geneva, Switzerland.
authors.forename: Vincent
authors.initials: V
authors.lastname: Kaddai
authors.affiliation: Institute of Social and Preventive Medicine, CHUV, Lausanne, Switzerland.
authors.forename: Murielle
authors.initials: M
authors.lastname: Bochud
authors.affiliation: Division of Clinical Pathology, University Hospitals, Geneva, Switzerland; Division of Gastroenterology and Hepatology, University Hospitals, Geneva, Switzerland. Electronic address: Francesco.Negro@hcuge.ch.
authors.forename: Francesco
authors.initials: F
authors.lastname: Negro
authors.affiliation: Infectious Diseases Service, Department of Medicine, University Hospital and University of Lausanne, Switzerland; Institute of Microbiology, University Hospital and University of Lausanne, Switzerland.
authors.forename: Pierre-Yves
authors.initials: PY
authors.lastname: Bochud
mesh_terms: D000328:Adult; D002352:Carrier Proteins / Q000235:genetics; D005234:Fatty Liver / Q000150:complications / Q000235:genetics* / Q000821:virology; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000821:virology*; D006801:Humans; D007372:Interferons; D007378:Interleukins / Q000235:genetics; D008049:Lipase / Q000235:genetics; D016015:Logistic Models; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D047495:PPAR gamma / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D012720:Severity of Illness Index; D000095022:Interferon Lambda; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent
chemical_list: D002352:Carrier Proteins; D007372:Interferons; D007378:Interleukins; D008049:Lipase; D008565:Membrane Proteins; D047495:PPAR gamma; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C106092:microsomal triglyceride transfer protein; C533682:PNPLA3 protein, human; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent