Document Detail


Genetic evidence for a role of adiponutrin in the metabolism of apolipoprotein B-containing lipoproteins.
MedLine Citation:
PMID:  19729411     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Adiponutrin (PNPLA3) is a predominantly liver-expressed transmembrane protein with phospholipase activity that is regulated by fasting and feeding. Recent genome-wide association studies identified PNPLA3 to be associated with hepatic fat content and liver function, thus pointing to a possible involvement in the hepatic lipoprotein metabolism. The aim of this study was to examine the association between two common variants in the adiponutrin gene and parameters of lipoprotein metabolism in 23,274 participants from eight independent West-Eurasian study populations including six population-based studies [Bruneck (n = 800), KORA S3/F3 (n = 1644), KORA S4/F4 (n = 1814), CoLaus (n = 5435), SHIP (n = 4012), Rotterdam (n = 5967)], the SAPHIR Study as a healthy working population (n = 1738) and the Utah Obesity Case-Control Study including a group of 1037 severely obese individuals (average BMI 46 kg/m2) and 827 controls from the same geographical region of Utah. We observed a strong additive association of a common non-synonymous variant within adiponutrin (rs738409) with age-, gender-, and alanine-aminotransferase-adjusted lipoprotein concentrations: each copy of the minor allele decreased levels of total cholesterol on average by 2.43 mg/dl (P = 8.87 x 10(-7)), non-HDL cholesterol levels by 2.35 mg/dl (P = 2.27 x 10(-6)) and LDL cholesterol levels by 1.48 mg/dl (P = 7.99 x 10(-4)). These associations remained significant after correction for multiple testing. We did not observe clear evidence for associations with HDL cholesterol or triglyceride concentrations. In conclusion, our study suggests that adiponutrin is involved in the metabolism of apoB-containing lipoproteins.
Authors:
Barbara Kollerits; Stefan Coassin; Noam D Beckmann; Alexander Teumer; Stefan Kiechl; Angela Döring; Maryam Kavousi; Steven C Hunt; Claudia Lamina; Bernhard Paulweber; Zoltán Kutalik; Matthias Nauck; Cornelia M van Duijn; Iris M Heid; Johann Willeit; Anita Brandstätter; Ted D Adams; Vincent Mooser; Yurii S Aulchenko; Henry Völzke; Florian Kronenberg
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2009-09-03
Journal Detail:
Title:  Human molecular genetics     Volume:  18     ISSN:  1460-2083     ISO Abbreviation:  Hum. Mol. Genet.     Publication Date:  2009 Dec 
Date Detail:
Created Date:  2009-11-05     Completed Date:  2010-02-12     Revised Date:  2011-03-03    
Medline Journal Info:
Nlm Unique ID:  9208958     Medline TA:  Hum Mol Genet     Country:  England    
Other Details:
Languages:  eng     Pagination:  4669-76     Citation Subset:  IM    
Affiliation:
Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Innsbruck Medical University, Innsbruck, Austria.
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Apolipoproteins B / metabolism*
Case-Control Studies
European Continental Ancestry Group / genetics
Female
Genetic Variation
Genome-Wide Association Study
Humans
Lipoproteins / metabolism
Male
Membrane Proteins / genetics,  metabolism*
Middle Aged
Obesity / genetics*,  metabolism*
Prospective Studies
Young Adult
Grant Support
ID/Acronym/Agency:
DK-55006/DK/NIDDK NIH HHS; M01-RR00064/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:
0/Apolipoproteins B; 0/Lipoproteins; 0/Membrane Proteins; 0/adiponutrin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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