Genetic evidence for a role of adiponutrin in the metabolism of apolipoprotein B-containing lipoproteins.
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.
Kollerits
Barbara
B
Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Innsbruck Medical University, Innsbruck, Austria.
Coassin
Stefan
S
Beckmann
Noam D
ND
Teumer
Alexander
A
Kiechl
Stefan
S
Döring
Angela
A
Kavousi
Maryam
M
Hunt
Steven C
SC
Lamina
Claudia
C
Paulweber
Bernhard
B
Kutalik
Zoltán
Z
Nauck
Matthias
M
van Duijn
Cornelia M
CM
Heid
Iris M
IM
Willeit
Johann
J
Brandstätter
Anita
A
Adams
Ted D
TD
Mooser
Vincent
V
Aulchenko
Yurii S
YS
Völzke
Henry
H
Kronenberg
Florian
F
D000328:Adult; D000368:Aged; D001055:Apolipoproteins B / Q000378:metabolism*; D016022:Case-Control Studies; D005260:Female; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D006801:Humans; D008074:Lipoproteins / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D009765:Obesity / Q000235:genetics* / Q000378:metabolism*; D011446:Prospective Studies; D044465:White People / Q000235:genetics; D055815:Young Adult
D001055:Apolipoproteins B; D008074:Lipoproteins; D008565:Membrane Proteins; C436316:adiponutrin