Apolipoprotein A-V, triglycerides and risk of coronary artery disease: the prospective Epic-Norfolk Population Study.
In mouse models, apolipoprotein A-V (apoA-V) exhibits triglyceride (TG)-lowering effects. We investigated the apoA-V/TG relationship and the association of apoA-V with coronary artery disease (CAD) risk by determining serum apoA-V levels and genotypes in a nested case-control (n = 1,034/2,031) study. Both univariate and multivariate apoA-V levels showed no association with future CAD (P = 0.4 and 0.5, respectively). Unexpectedly, there was a significant positive correlation between serum apoA-V and TG in men and women (r = 0.36 and 0.28, respectively, P < 0.001 each) but a negative correlation between apoA-V and LPL mass (r = -0.14 and -0.12 for men and women respectively, P < 0.001 each). The frequency of the c.56C>G polymorphism did not differ between cases and controls despite significant positive association of c.56G with both apoA-V and TG levels. For -1131T>C, the minor allele was significantly associated with lower apoA-V yet higher TG levels and was overrepresented in cases (P = 0.047). The association of -1131T>C with CAD risk, however, was independent of apoA-V levels and likely acts through linkage disequilibrium with APOC3 variants. The positive correlation of apoA-V levels with TG levels, negative correlation with LPL levels, and lack of association with CAD risk highlight the need for further human studies to clarify the role of apoA-V.
Vaessen
Stefan F C
SF
Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands.
Schaap
Frank G
FG
Kuivenhoven
Jan-Albert
JA
Groen
Albert K
AK
Hutten
Barbara A
BA
Boekholdt
S Matthijs
SM
Hattori
Hiroaki
H
Sandhu
Manjinder S
MS
Bingham
Sheila A
SA
Luben
Robert
R
Palmen
Jutta A
JA
Wareham
Nicholas J
NJ
Humphries
Steve E
SE
Kastelein
John J P
JJ
Talmud
Philippa J
PJ
Khaw
Kay-Tee
KT
D000368:Aged; D000072040:Apolipoprotein A-V; D001053:Apolipoproteins / Q000097:blood* / Q000235:genetics; D001054:Apolipoproteins A; D016022:Case-Control Studies; D003324:Coronary Artery Disease / Q000097:blood* / Q000235:genetics; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011446:Prospective Studies; D012307:Risk Factors; D014280:Triglycerides / Q000097:blood*; D006113:United Kingdom
C437704:APOA5 protein, human; D000072040:Apolipoprotein A-V; D001053:Apolipoproteins; D001054:Apolipoproteins A; D014280:Triglycerides