title: The PNPLA3 rs738409 C > G polymorphism is associated with the risk of progression to cirrhosis in NAFLD patients.
abstract: OBJECTIVE
  The patatin-like phospholipase domain-containing 3 (PNPLA3) rs738409 C > G single nucleotide polymorphism (SNP) has been associated with steatosis and fibrosis in previous NAFLD populations in which cirrhotic patients were very poorly represented. Since not all NAFLD with fibrosis evolve to cirrhosis, we investigated the specific risk of cirrhosis conferred in NAFLD patients by carrying this SNP.
  
  
  METHODS
  Three groups were studied: patients with NASH-cirrhosis; patients with biopsy-proven non-cirrhotic NAFLD; healthy subjects undergoing medicine check-ups. Epidemiological, anthropometric, and clinical data were collected, and the SNP was analyzed by pyrosequencing.
  
  
  RESULTS
  Sixty-one patients with NASH-cirrhosis, 60 with non-cirrhotic NAFLD, and 125 healthy controls were included. Frequency of the PNPLA3 minor (G) allele was increased in patients with NASH-cirrhosis compared with non-cirrhotic NAFLD and controls (allele frequency: 0.598 versus 0.367 versus 0.2, respectively, p < 0.001), and different between the latter two groups (p < 0.001). Three-quarters (74%) of NASH cirrhotics carried at least one G allele, and almost half of them (46%) were GG homozygous. By multivariate analysis in the NAFLD population, each copy of the G allele was associated with an almost doubling of the risk of cirrhosis [OR 1.8 (1.02-3.2)], while being GG homozygous with a tripled risk compared with being CC homozygous [3.01 (1.03-10.8)].
  
  
  CONCLUSIONS
  In NAFLD patients, carriage of the PNPLA3G allele, and particularly of the GG genotype, is significantly associated with the risk of cirrhotic evolution. If confirmed in larger series, these results would suggest that most of NASH cases require the contribution of an altered PNPLA3 function to progress until cirrhosis.
authors.affiliation: a Internal Medicine and Hepatology Unit , University Campus Bio-Medico , Rome , Italy ;
authors.forename: Umberto
authors.initials: U
authors.lastname: Vespasiani-Gentilucci
authors.affiliation: a Internal Medicine and Hepatology Unit , University Campus Bio-Medico , Rome , Italy ;
authors.forename: Paolo
authors.initials: P
authors.lastname: Gallo
authors.affiliation: a Internal Medicine and Hepatology Unit , University Campus Bio-Medico , Rome , Italy ;
authors.forename: Aldostefano
authors.initials: A
authors.lastname: Porcari
authors.affiliation: b Laboratory of Microscopic and Ultrastructural Anatomy, CIR , University Campus Bio-Medico , Rome , Italy ;
authors.forename: Simone
authors.initials: S
authors.lastname: Carotti
authors.affiliation: a Internal Medicine and Hepatology Unit , University Campus Bio-Medico , Rome , Italy ;
authors.forename: Giovanni
authors.initials: G
authors.lastname: Galati
authors.affiliation: c Virology Unit , University Campus Bio-Medico , Rome , Italy.
authors.forename: Livia
authors.initials: L
authors.lastname: Piccioni
authors.affiliation: a Internal Medicine and Hepatology Unit , University Campus Bio-Medico , Rome , Italy ;
authors.forename: Antonio
authors.initials: A
authors.lastname: De Vincentis
authors.affiliation: a Internal Medicine and Hepatology Unit , University Campus Bio-Medico , Rome , Italy ;
authors.forename: Chiara
authors.initials: C
authors.lastname: Dell'Unto
authors.affiliation: a Internal Medicine and Hepatology Unit , University Campus Bio-Medico , Rome , Italy ;
authors.forename: Ferruccio
authors.initials: F
authors.lastname: Vorini
authors.affiliation: b Laboratory of Microscopic and Ultrastructural Anatomy, CIR , University Campus Bio-Medico , Rome , Italy ;
authors.forename: Sergio
authors.initials: S
authors.lastname: Morini
authors.affiliation: c Virology Unit , University Campus Bio-Medico , Rome , Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Riva
authors.affiliation: a Internal Medicine and Hepatology Unit , University Campus Bio-Medico , Rome , Italy ;
authors.forename: Antonio
authors.initials: A
authors.lastname: Picardi
mesh_terms: D000328:Adult; D005260:Female; D005787:Gene Frequency; D006801:Humans; D008049:Lipase / Q000235:genetics*; D008099:Liver / Q000473:pathology; D008103:Liver Cirrhosis / Q000209:etiology*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease / Q000150:complications* / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent
chemical_list: D008049:Lipase; D008565:Membrane Proteins; C533682:PNPLA3 protein, human; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent
keywords: NASH cirrhosis; Non-alcoholic fatty liver disease; patatin-like phospholipase domain-containing 3