These authors contributed equally to this work.
Genetic variation in PNPLA3 but not APOC3 influences liver fat in non-alcoholic fatty liver disease
Version of Record online: 20 APR 2012
© 2011 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd
Journal of Gastroenterology and Hepatology
Volume 27, Issue 5, pages 951–956, May 2012
How to Cite
Hyysalo, J., Stojkovic, I., Kotronen, A., Hakkarainen, A., Sevastianova, K., Makkonen, J., Lundbom, N., Rissanen, A., Krauss, R. M., Melander, O., Orho-Melander, M. and Yki-Järvinen, H. (2012), Genetic variation in PNPLA3 but not APOC3 influences liver fat in non-alcoholic fatty liver disease. Journal of Gastroenterology and Hepatology, 27: 951–956. doi: 10.1111/j.1440-1746.2011.07045.x
- Issue online: 20 APR 2012
- Version of Record online: 20 APR 2012
- Accepted manuscript online: 6 DEC 2011 05:57AM EST
- Accepted for publication 21 November 2011.
- diabetes mellitus type 2;
- insulin resistance;
- metabolic syndrome;
- non-alcoholic fatty liver disease;
- proton magnetic resonance spectroscopy
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: 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.
Conclusion: Genetic variants in PNPLA3 but not APOC3 contribute to the variance in liver fat content due to NAFLD.