Patatin-like phospholipase 3 (rs738409) gene polymorphism is associated with increased liver enzymes in obese adolescents and metabolic syndrome in all ages.
BACKGROUND
Obesity is associated with non-alcoholic fatty liver disease (NAFLD), and the patatin-like phospholipase 3 (PNPLA3) rs738409 (Ile148Met, C>G) gene polymorphism is one of the most important genetic determinants of NAFLD. Carriers have been reported to better respond to lifestyle modification.


OBJECTIVE
To investigate the effect of rs738409 on overweight/obese adolescents and adults with and without metabolic syndrome (MetS).


METHODS
Two hundred and eighty-eight overweight/obese and 209 normal weight participants of the STYJOBS/EDECTA cohort (NCT00482924) were analysed for PNPLA3 genotypes.


RESULTS
Compared to overweight/obese without MetS, in overweight/obese study participants with MetS, the presence of the G allele (148Met) was significantly higher (CC: 5.0% vs. 9.2%, Spearman's correlation, 0.12; P = 0.038). Persons with CG (heterozygote for the risk allele) and with GG (homozygote for the risk allele) genotypes showed significantly higher ALT levels than those with CC genotypes. Even young individuals aged below 20 years had significantly increased ALT levels if they were homozygote with the G allele.


CONCLUSIONS
The PNPLA3 rs738409 polymorphism is associated already in youths with increased ALT, and is more frequent in obese with MetS of all ages. Hence, overweight/obese rs738409 carriers should be identified early in life and treated with a rigorous life style intervention.
Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria.|BioTechMed-Graz, Graz, Austria.
H
H
Mangge
Department of Internal Medicine, Metabolic Diseases and Medical Molecular Biology, Paracelsus Private Medical University, Salzburg, Austria.
B G
BG
Baumgartner
Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria.
S
S
Zelzer
Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria.
F
F
Prüller
General Practice for Internal Medicine, Bruck an der Mur, Austria.
W J
WJ
Schnedl
Department of Psychiatry, Medical University of Graz, Graz, Austria.
E Z
EZ
Reininghaus
Department of Pathology, Medical University of Graz, Graz, Austria.
J
J
Haybaeck
Department of Pathology, Medical University of Graz, Graz, Austria.
C
C
Lackner
Department of Internal Medicine, Medical University of Graz, Graz, Austria.
R
R
Stauber
First Department of Medicine, Paracelsus Medical University, Salzburg, Austria.|Obesity Research Unit, Paracelsus Medical University, Salzburg, Austria.
E
E
Aigner
Department of Pediatrics, Paracelsus Medical University, Salzburg, Austria.|Obesity Research Unit, Paracelsus Medical University, Salzburg, Austria.
D
D
Weghuber
D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D016022:Case-Control Studies; D002648:Child; D005260:Female; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D008019:Life Style; D008049:Lipase / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D024821:Metabolic Syndrome / Q000150:complications* / Q000235:genetics; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease / Q000235:genetics*; D009765:Obesity / Q000150:complications / Q000235:genetics*; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D055815:Young Adult; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent
D008049:Lipase; D008565:Membrane Proteins; C533682:PNPLA3 protein, human; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent