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 CaseeControl Study including a group of 1019 severely obese individuals (average body mass index 46.0 kg/m 2) 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=1.86310 9) and of AST concentration of 2.07 U/l (p=9.58310 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.
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