Genetic evidence for a role of adiponutrin in the metabolism of apolipoprotein B-containing lipoproteins.

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Serval ID
serval:BIB_AE758B021570
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Genetic evidence for a role of adiponutrin in the metabolism of apolipoprotein B-containing lipoproteins.
Journal
Human Molecular Genetics
Author(s)
Kollerits B., Coassin S., Beckmann N.D., Teumer A., Kiechl S., Döring A., Kavousi M., Hunt S.C., Lamina C., Paulweber B., Kutalik Z., Nauck M., van Duijn C.M., Heid I.M., Willeit J., Brandstätter A., Adams T.D., Mooser V., Aulchenko Y.S., Völzke H., Kronenberg F.
ISSN
1460-2083[electronic]
Publication state
Published
Issued date
2009
Volume
18
Number
23
Pages
4669-4676
Language
english
Abstract
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.
Keywords
Human Adipose-Tissue, Protein Function, Family-Members, Plasma-Levels, Expression, Obesity, Liver, Identification, Triglycerides, Cholesterol , Colaus Study
Pubmed
Web of science
Open Access
Yes
Create date
24/11/2009 16:14
Last modification date
25/09/2019 6:10
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