title: PNPLA 3 I148M genetic variant associates with insulin resistance and baseline viral load in HCV genotype 2 but not in genotype 3 infection.
abstract: BACKGROUND
  Hepatic steatosis in HCV patients has been postulated as a risk factor associated with a higher frequency of fibrosis and cirrhosis. A single genetic variant, PNPLA3 I148M, has been widely associated with increased hepatic steatosis. Previous studies of the PNPLA3 I148M sequence variant in HCV infected individuals have reported an association between this variant and prevalence of steatosis, fibrosis, and cirrhosis. To evaluate the impact of PNPLA3 I148M variant on metabolic traits and treatment response in HCV genotype 2 and 3 infected patients.
  
  
  METHODS
  Three hundred and eighty-two treatment naïve HCV genotype 2 or 3 infected patients were included in a phase III, open label, randomized, multicenter, investigator-initiated trial (the NORDynamIC study), in which pretreatment liver biopsies were mandatory. PNPLA3I148M genotyping was performed in a total of 359 Caucasian patients.
  
  
  RESULTS
  In HCV genotype 2 infected patients carrying the PNPLA3 148M allele, there was significantly increased insulin resistance (P = 0.023) and lower viral load (P = 0.005) at baseline as well as the first seven days of antiviral treatment. These results were not observed in HCV genotype 3 infected patients.
  
  
  CONCLUSIONS
  Our results suggest a possible association between the PNPLA3 148M allele and insulin resistance as well as baseline viral load in HCV genotype 2, but not in genotype 3.
authors.affiliation: Department of Infectious Diseases/Virology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Karolina
authors.initials: K
authors.lastname: Rembeck
authors.forename: Cristina
authors.initials: C
authors.lastname: Maglio
authors.forename: Martin
authors.initials: M
authors.lastname: Lagging
authors.forename: Peer Brehm
authors.initials: PB
authors.lastname: Christensen
authors.forename: Martti
authors.initials: M
authors.lastname: Färkkilä
authors.forename: Nina
authors.initials: N
authors.lastname: Langeland
authors.forename: Mads Rauning
authors.initials: MR
authors.lastname: Buhl
authors.forename: Court
authors.initials: C
authors.lastname: Pedersen
authors.forename: Kristine
authors.initials: K
authors.lastname: Mørch
authors.forename: Gunnar
authors.initials: G
authors.lastname: Norkrans
authors.forename: Kristoffer
authors.initials: K
authors.lastname: Hellstrand
authors.forename: Magnus
authors.initials: M
authors.lastname: Lindh
authors.forename: Carlo
authors.initials: C
authors.lastname: Pirazzi
authors.forename: Maria Antonella
authors.initials: MA
authors.lastname: Burza
authors.forename: Stefano
authors.initials: S
authors.lastname: Romeo
authors.forename: Johan
authors.initials: J
authors.lastname: Westin
mesh_terms: D000328:Adult; D000483:Alleles; D000998:Antiviral Agents / Q000627:therapeutic use; D005234:Fatty Liver / Q000150:complications / Q000235:genetics; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000150:complications* / Q000188:drug therapy / Q000821:virology; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics*; D008049:Lipase / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D019562:Viral Load; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent
chemical_list: D000998:Antiviral Agents; D008049:Lipase; D008565:Membrane Proteins; C533682:PNPLA3 protein, human; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent