title: Genetic variation in PNPLA3 but not APOC3 influences liver fat in non-alcoholic fatty liver disease.
abstract: OBJECTIVE
  A recent study in Indian subjects suggested common variants in apolipoprotein C3 (APOC3) (T-455C at rs2854116 and C-482T at rs2854117) to contribute to non-alcoholic fatty liver disease (NAFLD), plasma apoC3 and triglyceride concentrations. Our aim was to determine the contribution of genetic variation in APOC3 on liver fat content and plasma triglyceride and apoC3 concentrations in a larger European cohort.
  
  
  METHODS
  A total of 417 Finnish individuals were genotyped for rs2854116 and rs2854117 in APOC3 and the known rs738409 in patatin-like phospholipase domain-containing protein 3 (PNPLA3) influencing liver fat. Plasma apoC3 concentration was measured enzymatically, and liver fat by proton magnetic resonance spectroscopy.
  
  
  RESULTS
  APOC3 wild-type homozygotes and variant allele (T-455C or C-482T or both) carriers did not differ with regard to liver fat, apoC3 concentrations, triglyceride-, high density lipoprotein-, fasting plasma glucose, insulin-, alanine aminotransferase- and aspartate aminotransferase-concentrations, nor was there a difference in prevalence of NAFLD. In contrast, carriers of the PNPLA3 GG genotype at rs738409 had a 2.7-fold (median 11.3%) higher liver fat than those with the CC (median 4.2%) genotype. The PNPLA3 rs738409 was also an independent predictor of liver fat, together with age, gender, and body mass index.
  
  
  CONCLUSIONS
  Genetic variants in PNPLA3 but not APOC3 contribute to the variance in liver fat content due to NAFLD.
authors.affiliation: Department of Medicine, Division of Diabetes, Helsinki University Central Hospital, Finland.
authors.forename: Jenni
authors.initials: J
authors.lastname: Hyysalo
authors.forename: Ivana
authors.initials: I
authors.lastname: Stojkovic
authors.forename: Anna
authors.initials: A
authors.lastname: Kotronen
authors.forename: Antti
authors.initials: A
authors.lastname: Hakkarainen
authors.forename: Ksenia
authors.initials: K
authors.lastname: Sevastianova
authors.forename: Janne
authors.initials: J
authors.lastname: Makkonen
authors.forename: Nina
authors.initials: N
authors.lastname: Lundbom
authors.forename: Aila
authors.initials: A
authors.lastname: Rissanen
authors.forename: Ronald M
authors.initials: RM
authors.lastname: Krauss
authors.forename: Olle
authors.initials: O
authors.lastname: Melander
authors.forename: Marju
authors.initials: M
authors.lastname: Orho-Melander
authors.forename: Hannele
authors.initials: H
authors.lastname: Yki-Järvinen
mesh_terms: D000328:Adult; D000367:Age Factors; D000410:Alanine Transaminase / Q000097:blood; D000483:Alleles; D000704:Analysis of Variance; D053305:Apolipoprotein C-III / Q000097:blood / Q000235:genetics*; D001219:Aspartate Aminotransferases / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D015992:Body Mass Index; D005234:Fatty Liver / Q000235:genetics* / Q000473:pathology*; D005260:Female; D005387:Finland; D006720:Homozygote; D006801:Humans; D007328:Insulin / Q000097:blood; D050152:Intra-Abdominal Fat; D008049:Lipase / Q000235:genetics*; D008075:Lipoproteins, HDL / Q000097:blood; D008099:Liver / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease; D020641:Polymorphism, Single Nucleotide; D012737:Sex Factors; D018709:Statistics, Nonparametric; D014280:Triglycerides / Q000097:blood; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent
chemical_list: D000410:Alanine Transaminase; D053305:Apolipoprotein C-III; D001219:Aspartate Aminotransferases; D001786:Blood Glucose; D007328:Insulin; D008049:Lipase; D008075:Lipoproteins, HDL; D008565:Membrane Proteins; D014280:Triglycerides; C533682:PNPLA3 protein, human; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent