Genetic variation in PNPLA3 but not APOC3 influences liver fat in non-alcoholic fatty liver disease

Research output: Contribution to journalArticle


Background and Aim: 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: Atotal 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. Conclusion: Genetic variants in PNPLA3 but not APOC3 contribute to the variance in liver fat content due to NAFLD.


  • Jenni Hyysalo
  • Ivana Stojkovic
  • Anna Kotronen
  • Antti Hakkarainen
  • Ksenia Sevastianova
  • Janne Makkonen
  • Nina Lundbom
  • Aila Rissanen
  • Ronald M. Krauss
  • Olle Melander
  • Marju Orho-Melander
  • Hannele Yki-Jarvinen
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Gastroenterology and Hepatology


  • diabetes mellitus type 2, insulin resistance, metabolic syndrome, non-alcoholic fatty liver disease, proton magnetic resonance, spectroscopy
Original languageEnglish
Pages (from-to)951-956
JournalJournal of Gastroenterology and Hepatology
Issue number5
Publication statusPublished - 2012
Publication categoryResearch

Related research output

Ivana Stojkovic, 2015, Diabetes and cardiovascular disease - genetic epidemiology. 156 p.

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