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A common variant in the adiponutrin gene influences liver enzyme values
  1. Barbara Kollerits1,
  2. Stefan Coassin1,
  3. Stefan Kiechl2,
  4. Steven C Hunt3,
  5. Bernhard Paulweber4,
  6. Johann Willeit2,
  7. Anita Brandstätter1,
  8. Claudia Lamina1,
  9. Ted D Adams3,
  10. Florian Kronenberg1
  1. 1Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Innsbruck Medical University, Innsbruck, Austria
  2. 2Department of Neurology, Innsbruck Medical University, Innsbruck, Austria
  3. 3Cardiovascular Genetics Division, University of Utah School of Medicine, Salt Lake City, Utah, USA
  4. 4First Department of Internal Medicine, Paracelsus Private Medical University Salzburg, Austria
  1. Correspondence to Florian Kronenberg, Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Innsbruck Medical University, Schöpfstr. 41, A-6020 Innsbruck, Austria; florian.kronenberg{at}


Background Two recent genome-wide association studies identified the liver expressed transmembrane protein adiponutrin to be associated with liver related phenotypes such as non-alcoholic fatty liver disease and liver function enzymes. These associations were not uniformly reported for various ethnicities. The aim of this study was to investigate a common non-synonymous variant within adiponutrin (rs738409, exon 3) with parameters of liver function in three independent West Eurasian study populations including a total of 4290 participants.

Methods The study was performed in (1) the population based Bruneck Study (n=783), (2) the Salzburg Atherosclerosis Prevention Program in Subjects at High Individual Risk Study from Austria based on a healthy working population (n=1705), and the Utah Obesity Case–Control Study including a group of 1019 severely obese individuals (average body mass index 46.0 kg/m2) and 783 controls from the same geographical region of Utah. Liver enzymes measured were alanine aminotransferase (ALT), aspartate aminotransferase (AST) and γ-glutamyl transferase (GGT).

Results A strong recessive association of this polymorphism was found with age and gender adjusted ALT and AST concentrations: being homozygous for the minor allele resulted in a highly significant increase of ALT concentration of 3.53 U/l (p=1.86×10−9) and of AST concentration of 2.07 U/l (p=9.58×10−6), respectively. The associations were consistently found in all three study populations.

Conclusion The highly significant associations of this transversion polymorphism within the adiponutrin gene with increased ALT and AST concentrations support a role for adiponutrin as a susceptibility gene for hepatic dysfunction.

  • PNPLA3
  • rs738409
  • genetic association
  • hepatic dysfunction
  • adiponutrin
  • liver enzymes
  • alanine-aminotransferase
  • association study
  • endocrinology
  • metabolic disorders
  • liver disease
  • genetic epidemiology

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  • Supplementary tables 1–3 are published online only at

  • Funding This work was supported by grants from the ‘Genomics of Lipid-associated Disorders – GOLD’ of the ‘Austrian Genome Research Programme GEN-AU’ to F Kronenberg, by a grant from the National Institute of Diabetes and Digestive and Kidney Diseases (DK-55006), and a grant from the National Center for Research Resources (M01-RR00064). Other funders: NIH.

  • Competing interests None.

  • Ethics approval This study was conducted with the approval of the University of Salt Lake City; University of Innsbruck.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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