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

Barbara Kollerits, Stefan Coassin, Noam D. Beckmann, Alexander Teumer, Stefan Kiechl, Angela Döring, Maryam Kavousi, Steven 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 & 1 others Florian Kronenberg

Research output: Contribution to journalArticle

41 Citations (Scopus)

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 × 10-7), non-HDL cholesterol levels by 2.35 mg/dl (P = 2.27 × 10-6) and LDL cholesterol levels by 1.48 mg/dl (P = 7.99 × 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.

Original languageEnglish
Pages (from-to)4669-4676
Number of pages8
JournalHuman Molecular Genetics
Volume18
Issue number23
DOIs
Publication statusPublished - 2009
Externally publishedYes

Fingerprint

Apolipoproteins B
Lipoproteins
Liver
Cholesterol
Population
Phospholipases
Genome-Wide Association Study
Alanine Transaminase
LDL Cholesterol
HDL Cholesterol
Case-Control Studies
Fasting
Triglycerides
Obesity
Fats
Alleles
adiponutrin
Genes
Proteins

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)
  • Molecular Biology

Cite this

Kollerits, B., Coassin, S., Beckmann, N. D., Teumer, A., Kiechl, S., Döring, A., ... Kronenberg, F. (2009). Genetic evidence for a role of adiponutrin in the metabolism of apolipoprotein B-containing lipoproteins. Human Molecular Genetics, 18(23), 4669-4676. https://doi.org/10.1093/hmg/ddp424

Genetic evidence for a role of adiponutrin in the metabolism of apolipoprotein B-containing lipoproteins. / Kollerits, Barbara; Coassin, Stefan; Beckmann, Noam D.; Teumer, Alexander; Kiechl, Stefan; Döring, Angela; Kavousi, Maryam; Hunt, Steven; Lamina, Claudia; Paulweber, Bernhard; Kutalik, Zoltán; Nauck, Matthias; van Duijn, Cornelia M.; Heid, Iris M.; Willeit, Johann; Brandstätter, Anita; Adams, Ted D.; Mooser, Vincent; Aulchenko, Yurii S.; Völzke, Henry; Kronenberg, Florian.

In: Human Molecular Genetics, Vol. 18, No. 23, 2009, p. 4669-4676.

Research output: Contribution to journalArticle

Kollerits, B, Coassin, S, Beckmann, ND, Teumer, A, Kiechl, S, Döring, A, Kavousi, M, Hunt, S, Lamina, C, Paulweber, B, Kutalik, Z, Nauck, M, van Duijn, CM, Heid, IM, Willeit, J, Brandstätter, A, Adams, TD, Mooser, V, Aulchenko, YS, Völzke, H & Kronenberg, F 2009, 'Genetic evidence for a role of adiponutrin in the metabolism of apolipoprotein B-containing lipoproteins', Human Molecular Genetics, vol. 18, no. 23, pp. 4669-4676. https://doi.org/10.1093/hmg/ddp424
Kollerits, Barbara ; Coassin, Stefan ; Beckmann, Noam D. ; Teumer, Alexander ; Kiechl, Stefan ; Döring, Angela ; Kavousi, Maryam ; Hunt, Steven ; Lamina, Claudia ; Paulweber, Bernhard ; Kutalik, Zoltán ; Nauck, Matthias ; van Duijn, Cornelia M. ; Heid, Iris M. ; Willeit, Johann ; Brandstätter, Anita ; Adams, Ted D. ; Mooser, Vincent ; Aulchenko, Yurii S. ; Völzke, Henry ; Kronenberg, Florian. / Genetic evidence for a role of adiponutrin in the metabolism of apolipoprotein B-containing lipoproteins. In: Human Molecular Genetics. 2009 ; Vol. 18, No. 23. pp. 4669-4676.
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