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

Authors

  • Jenni Hyysalo,

    1. Department of Medicine, Division of Diabetes, Helsinki University Central Hospital, Finland
    2. Minerva Foundation Institute for Medical Research, Helsinki, Finland
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    • These authors contributed equally to this work.

  • Ivana Stojkovic,

    1. Department of Clinical Sciences, Diabetes and Endocrinology, University Hospital Malmö, Lund University, Malmö, Sweden
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    • These authors contributed equally to this work.

  • Anna Kotronen,

    1. Department of Medicine, Division of Diabetes, Helsinki University Central Hospital, Finland
    2. Minerva Foundation Institute for Medical Research, Helsinki, Finland
    3. Diabetes Prevention Unit, National Institute for health and Welfare, Helsinki, Finland
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  • Antti Hakkarainen,

    1. Department of Medicine, Division of Diabetes, Helsinki University Central Hospital, Finland
    2. Department of Radiology, Helsinki University Central Hospital, Finland
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  • Ksenia Sevastianova,

    1. Department of Medicine, Division of Diabetes, Helsinki University Central Hospital, Finland
    2. Minerva Foundation Institute for Medical Research, Helsinki, Finland
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  • Janne Makkonen,

    1. Department of Medicine, Division of Diabetes, Helsinki University Central Hospital, Finland
    2. Minerva Foundation Institute for Medical Research, Helsinki, Finland
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  • Nina Lundbom,

    1. Department of Radiology, Helsinki University Central Hospital, Finland
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  • Aila Rissanen,

    1. Obesity Research Unit, Department of Psychiatry, Helsinki University Central Hospital, Finland
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  • Ronald M Krauss,

    1. Department of Clinical Sciences, Diabetes and Endocrinology, University Hospital Malmö, Lund University, Malmö, Sweden
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  • Olle Melander,

    1. Department of Clinical Sciences, Diabetes and Endocrinology, University Hospital Malmö, Lund University, Malmö, Sweden
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  • Marju Orho-Melander,

    1. Department of Clinical Sciences, Diabetes and Endocrinology, University Hospital Malmö, Lund University, Malmö, Sweden
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  • Hannele Yki-Järvinen

    Corresponding author
    1. Department of Medicine, Division of Diabetes, Helsinki University Central Hospital, Finland
      Professor Hannele Yki-Järvinen, Department of Medicine, Division of Diabetes, University of Helsinki, P.O. Box 700, Room C425B, FIN-00029 HUCH Helsinki, Finland. Email: ykijarvi@cc.helsinki.fi
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Professor Hannele Yki-Järvinen, Department of Medicine, Division of Diabetes, University of Helsinki, P.O. Box 700, Room C425B, FIN-00029 HUCH Helsinki, Finland. Email: ykijarvi@cc.helsinki.fi

Abstract

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.

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