title: A gene variant of PNPLA3, but not of APOC3, is associated with histological parameters of NAFLD in an obese population.
abstract: OBJECTIVE
  Mechanisms explaining the relationship in non-alcoholic fatty liver disease (NAFLD), obesity, and insulin resistance are poorly understood. A genetic basis has been suggested. We studied the association between the genes patatin-like phospholipase domain-containing protein 3 (PNPLA3) and apolipoprotein C3 (APOC3) and metabolic and histological parameters of NAFLD in obese patients.
  
  
  METHODS
  Overweight and obese patients underwent a metabolic and liver assessment. If NAFLD was suspected, liver biopsy was proposed. APOC3 variant rs2854117 and PNPLA3 variant rs738409 were genotyped.
  
  
  RESULTS
  Four hundred seventy patients were included (61.1% had liver biopsy). The percentage of patients with non-alcoholic steatohepatitis (NASH) was significantly different according to the PNPLA3 variant. After adjustment for age and body mass index, the PNPLA3 variant was associated with alanine aminotransferase (P < 0.001) and aspartate aminotransferase (P < 0.001). The PNPLA3 variant was associated with more severe features of steatohepatitis: steatosis (P < 0.001), lobular inflammation (P < 0.001), and ballooning (P = 0.002), but not with liver fibrosis, anthropometry, or insulin resistance. No significant difference in liver histology, anthropometric, or metabolic parameters was found between carriers and non-carriers of the APOC3 variant.
  
  
  CONCLUSIONS
  PNPLA3 polymorphism rs738409 was associated with NASH and the severity of necroinflammatory changes independently of metabolic factors. No association between APOC3 gene variant rs2854117 and histological or metabolic parameters of NAFLD was found.
authors.affiliation: Department of Endocrinology, Diabetology and Metabolism, Antwerp University Hospital, University of Antwerp, Belgium.
authors.forename: A
authors.initials: A
authors.lastname: Verrijken
authors.forename: S
authors.initials: S
authors.lastname: Beckers
authors.forename: S
authors.initials: S
authors.lastname: Francque
authors.forename: H
authors.initials: H
authors.lastname: Hilden
authors.forename: S
authors.initials: S
authors.lastname: Caron
authors.forename: D
authors.initials: D
authors.lastname: Zegers
authors.forename: M
authors.initials: M
authors.lastname: Ruppert
authors.forename: G
authors.initials: G
authors.lastname: Hubens
authors.forename: E
authors.initials: E
authors.lastname: Van Marck
authors.forename: P
authors.initials: P
authors.lastname: Michielsen
authors.forename: B
authors.initials: B
authors.lastname: Staels
authors.forename: M-R
authors.initials: MR
authors.lastname: Taskinen
authors.forename: W
authors.initials: W
authors.lastname: Van Hul
authors.forename: L
authors.initials: L
authors.lastname: Van Gaal
mesh_terms: D000328:Adult; D000410:Alanine Transaminase / Q000235:genetics / Q000378:metabolism; D053305:Apolipoprotein C-III / Q000235:genetics* / Q000378:metabolism; D001219:Aspartate Aminotransferases / Q000235:genetics / Q000378:metabolism; D015992:Body Mass Index; D003430:Cross-Sectional Studies; D005234:Fatty Liver / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D050152:Intra-Abdominal Fat / Q000378:metabolism; D008049:Lipase / Q000235:genetics* / Q000378:metabolism; D050356:Lipid Metabolism / Q000235:genetics; D008099:Liver / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease; D009765:Obesity / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent
chemical_list: D000410:Alanine Transaminase; D053305:Apolipoprotein C-III; D001219:Aspartate Aminotransferases; D008049:Lipase; D008565:Membrane Proteins; C533682:PNPLA3 protein, human; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent