A common variant in the adiponutrin gene influences liver enzyme values.
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/m(2)) and 783 controls from the same geographical region of Utah. Liver enzymes measured were alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-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 x 10(-9)) and of AST concentration of 2.07 U/l (p=9.58 x 10(-6)), respectively. The associations were consistently found in all three study populations.


CONCLUSIONS
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.
Kollerits
Barbara
B
Coassin
Stefan
S
Kiechl
Stefan
S
Hunt
Steven C
SC
Paulweber
Bernhard
B
Willeit
Johann
J
Brandstätter
Anita
A
Lamina
Claudia
C
Adams
Ted D
TD
Kronenberg
Florian
F
D000328:Adult; D000410:Alanine Transaminase / Q000097:blood*; D001219:Aspartate Aminotransferases / Q000097:blood*; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study / Q000379:methods; D005838:Genotype; D006801:Humans; D016014:Linear Models; D008049:Lipase / Q000235:genetics* / Q000378:metabolism; D008099:Liver / Q000201:enzymology*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D009765:Obesity; D005723:gamma-Glutamyltransferase / Q000097:blood*; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent
D000410:Alanine Transaminase; D001219:Aspartate Aminotransferases; D008049:Lipase; D008565:Membrane Proteins; D005723:gamma-Glutamyltransferase; C533682:PNPLA3 protein, human; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent